1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Immunology
  4. Volume 31, 2013
  5. Article

Annual Review of Immunology

Volume 31, 2013

Years in Cologne

Abstract

This review describes the building and scientific activity of the Immunology Department at the Institute for Genetics in Cologne, cofounded by Max Delbrück in post–World War II Germany. The protagonist, a child of Russian emigrants, became interested in antibodies as a postdoc at the Pasteur Institute in Paris and a proponent of the antigen-bridge model of T-B cell collaboration during his early time in Cologne. He was challenged by the gap between cellular immunology and molecular genetics and profited from the advances of the latter as well as postwar economic growth in Germany. The Immunology Department became a place, and little universe in itself, where young scientists from all over the world came together to study cellular and molecular mechanisms of antibody formation. This included work on normal and malignant B cells in the human, particularly the origin of Hodgkin lymphoma, but the main focus was on B cell development and homeostasis, the germinal center reaction, and immunological memory, developing recombinase-assisted and conditional gene targeting in mice as a main technical tool.

Keyword(s): Autobiography, B cell development, B cell lymphomas, conditional gene targeting, germinal centers, Hodgkin lymphoma, memory B cells, T-B collaboration
Loading

Article metrics loading...

/content/journals/10.1146/annurev.immunol.021908.132646
2013-03-21
2025-04-27
Loading full text...

Full text loading...

/deliver/fulltext/immunol/31/1/annurev.immunol.021908.132646.html?itemId=/content/journals/10.1146/annurev.immunol.021908.132646&mimeType=html&fmt=ahah

Literature Cited

  1. Benjamin W. 1.  1935. Paris, Die Hauptstadt des XIX. Jahrhunderts. Walter Benjamin, Gesammelte Schriften R Tiedemann, V:45 Suhrkamp: Frankfurt [Google Scholar]
  2. Sombart N. 2.  1994. Pariser Lehrjahre Hamburg: Hoffmann und Campe [Google Scholar]
  3. Appella E, Markert CL. 3.  1961. Dissociation of lactate dehydrogenase into subunits with guanidine hydrochloride. Biochem. Biophys. Res. Commun. 6:171–76 [Google Scholar]
  4. Cahn RD, Zwilling E, Kaplan NO, Levine L. 4.  1962. Nature and development of lactic dehydrogenases. Science 136:962–69 [Google Scholar]
  5. Sterzl J. 5.  1964. Molecular and Cellular Basis of Antibody Formation: Proceedings of the Symposium held in Prague on June 1–5, 1964 Prague: Publ. House Czechoslov. Acad. Sci. [Google Scholar]
  6. Rajewsky K. 6.  1966. Rabbit antibody to pig lactic dehydrogenase reacting with the rabbit's own enzyme. Immunochemistry 3:487–89 [Google Scholar]
  7. Rajewsky K, Rottländer E, Peltre G, Müller B. 7.  1967. The immune response to a hybrid protein molecule; specificity of secondary stimulation and of tolerance induction. J. Exp. Med. 126:4581–606 [Google Scholar]
  8. Jerne NK. 8.  1955. The natural-selection theory of antibody formation. Proc. Natl. Acad. Sci. USA 41:11849–57 [Google Scholar]
  9. Rajewsky K, Rottländer E. 9.  1967. Tolerance specificity and the immune response to lactic dehydrogenase isoenzymes. Cold Spring Harb. Symp. Quant. Biol. 32:547–54 [Google Scholar]
  10. Mitchison NA. 10.  1967. Antigen recognition responsible for the induction in vitro of the secondary response. Cold Spring Harb. Symp. Quant. Biol. 32:431–39 [Google Scholar]
  11. Jerne NK. 11.  1967. Summary: waiting for the end. Cold Spring Harb. Symp. Quant. Biol. 32:591–603 [Google Scholar]
  12. Rajewsky K, Schirrmacher V, Nase S, Jerne NK. 12.  1969. The requirement of more than one antigenic determinant for immunogenicity. J. Exp. Med. 129:61131–43 [Google Scholar]
  13. Claman HN, Chaperon EA, Triplett RF. 13.  1966. Thymus-marrow cell combinations. Synergism in antibody production. Proc. Soc. Exp. Biol. Med. 122:41167–71 [Google Scholar]
  14. Mitchell GF, Miller JF. 14.  1968. Cell to cell interaction in the immune response. II. The source of hemolysin-forming cells in irradiated mice given bone marrow and thymus or thoracic duct lymphocytes. J. Exp. Med. 128:4821–37 [Google Scholar]
  15. Rajewsky K. 15.  1971. The carrier effect and cellular cooperation in the induction of antibodies. Proc. R. Soc. Lond. B Biol. Sci. 176:45385–92 [Google Scholar]
  16. Mitchison NA, Rajewsky K, Taylor RB. 16.  1970. Cooperation of antigenic determinants and of cells in the induction of antibodies. Proceedings of the Prague Symposium on Developmental Aspects of Antibody Formation and Structure Prague: Publ. House Czechoslov. Acad. Sci. [Google Scholar]
  17. Mitchison NA. 17.  2004. T-cell-B-cell cooperation. Nat. Rev. Immunol. 4:4308–12 [Google Scholar]
  18. Raff MC. 18.  1970. Role of thymus-derived lymphocytes in the secondary humoral immune response in mice. Nature 226:52521257–58 [Google Scholar]
  19. Chesnut RW, Grey HM. 19.  1981. Studies on the capacity of B cells to serve as antigen-presenting cells. J. Immunol. 126:31075–79 [Google Scholar]
  20. Lanzavecchia A. 20.  1985. Antigen-specific interaction between T and B cells. Nature 314:6011537–39 [Google Scholar]
  21. Oudin J, Michel M. 21.  1969. Idiotypy of rabbit antibodies. I. Comparison of idiotypy of antibodies against Salmonella typhi with that of antibodies against other bacteria in the same rabbits, or of antibodies against Salmonella typhi in various rabbits. J. Exp. Med. 130:3595–617 [Google Scholar]
  22. Oudin J, Michel M. 22.  1969. Idiotypy of rabbit antibodies. II. Comparison of idiotypy of various kinds of antibodies formed in the same rabbits against Salmonella typhi. J. Exp. Med. 130:3619–42 [Google Scholar]
  23. Mäkelä O, Karjalainen K. 23.  1977. Inherited immunoglobulin idiotypes of the mouse. Immunol. Rev. 34:119–38 [Google Scholar]
  24. Eichmann K. 24.  1973. Idiotype expression and the inheritance of mouse antibody clones. J. Exp. Med. 137:3603–21 [Google Scholar]
  25. Jerne NK. 25.  1974. Towards a network theory of the immune system. Ann. Immunol. (Paris) 125C:1–2373–89 [Google Scholar]
  26. Eichmann K. 26.  1974. Idiotype suppression. I. Influence of the dose and of the effector functions of anti-idiotypic antibody on the production of an idiotype. Eur. J. Immunol. 4:4296–302 [Google Scholar]
  27. Eichmann K. 27.  1975. Idiotype suppression. II. Amplification of a suppressor T cell with anti-idiotypic activity. Eur. J. Immunol. 5:8511–17 [Google Scholar]
  28. Eichmann K, Rajewsky K. 28.  1975. Induction of T and B cell immunity by anti-idiotypic antibody. Eur. J. Immunol. 5:10661–66 [Google Scholar]
  29. Rajewsky K, Mohr R. 29.  1974. Specificity and heterogeneity of helper T cells in the response to serum albumins in mice. Eur. J. Immunol. 4:2111–19 [Google Scholar]
  30. Imanishi T, Mäkelä O. 30.  1973. Strain differences in the fine specificity of mouse anti-hapten antibodies. Eur. J. Immunol. 3:6323–30 [Google Scholar]
  31. Imanishi T, Mäkelä O. 31.  1974. Inheritance of antibody specificity. I. Anti-(4-hydroxy-3-nitrophenyl)acetyl of the mouse primary response. J. Exp. Med. 140:61498–510 [Google Scholar]
  32. Jack RS, Imanishi-Kari T, Rajewsky K. 32.  1977. Idiotypic analysis of the response of C57BL/6 mice to the (4-hydroxy-3-nitrophenyl)acetyl group. Eur. J. Immunol. 7:8559–65 [Google Scholar]
  33. Krawinkel U, Cramer M, Imanishi-Kari T, Jack RS, Rajewsky K, Mäkelä O. 33.  1977. Isolated hapten-binding receptors of sensitized lymphocytes. I. Receptors from nylon wool-enriched mouse T lymphocytes lack serological markers of immunoglobulin constant domains but express heavy chain variable portions. Eur. J. Immunol. 7:8566–73 [Google Scholar]
  34. Cramer M, Krawinkel U, Melchers I, Imanishi-Kari T, Ben-Neriah Y. 34.  et al. 1979. Isolated hapten-binding receptors of sensitized lymphocytes. IV. Expression of immunoglobulin variable regions in (4-hydroxy-3-nitrophenyl) acetyl (NP)-specific receptors isolated from murine B and T lymphocytes. Eur. J. Immunol. 9:4332–38 [Google Scholar]
  35. Black SJ, Hämmerling GJ, Berek C, Rajewsky K, Eichmann K. 35.  1976. Idiotypic analysis of lymphocytes in vitro. I. Specificity and heterogeneity of B and T lymphocytes reactive with anti-idiotypic antibody. J. Exp. Med. 143:4846–60 [Google Scholar]
  36. Binz H, Wigzell H. 36.  1975. Shared idiotypic determinants on B and T lymphocytes reactive against the same antigenic determinants. I. Demonstration of similar or identical idiotypes on IgG molecules and T-cell receptors with specificity for the same alloantigens. J. Exp. Med. 142:1197–211 [Google Scholar]
  37. Binz H, Wigzell H, Bazin H. 37.  1976. T-cell idiotypes are linked to immunoglobulin heavy chain genes. Nature 264:5587639–42 [Google Scholar]
  38. Rajewsky K. 38.  1983. Cross-reacting idiotypes on antibodies and T cell receptors: How can the data be interpreted?. Scand. J. Immunol. 18:96 [Google Scholar]
  39. Hedrick SM, Cohen DI, Nielsen EA, Davis MM. 39.  1984. Isolation of cDNA clones encoding T cell-specific membrane-associated proteins. Nature 308:5955149–53 [Google Scholar]
  40. Hedrick SM, Nielsen EA, Kavaler J, Cohen DI, Davis MM. 40.  1984. Sequence relationships between putative T-cell receptor polypeptides and immunoglobulins. Nature 308:5955153–58 [Google Scholar]
  41. Yanagi Y, Yoshikai Y, Leggett K, Clark SP, Aleksander I, Mak TW. 41.  1984. A human T cell-specific cDNA clone encodes a protein having extensive homology to immunoglobulin chains. Nature 308:5955145–49 [Google Scholar]
  42. Hozumi N, Tonegawa S. 42.  1976. Evidence for somatic rearrangement of immunoglobulin genes coding for variable and constant regions. Proc. Natl. Acad. Sci. USA 73:103628–32 [Google Scholar]
  43. Sakano H, Maki R, Kurosawa Y, Roeder W, Tonegawa S. 43.  1980. Two types of somatic recombination are necessary for the generation of complete immunoglobulin heavy-chain genes. Nature 286:5774676–83 [Google Scholar]
  44. Honjo T, Kataoka T. 44.  1978. Organization of immunoglobulin heavy chain genes and allelic deletion model. Proc. Natl. Acad. Sci. USA 75:52140–44 [Google Scholar]
  45. Alt FW, Yancopoulos GD, Blackwell TK, Wood C, Thomas E. 45.  et al. 1984. Ordered rearrangement of immunoglobulin heavy chain variable region segments. EMBO J. 3:61209–19 [Google Scholar]
  46. Köhler G, Milstein C. 46.  1975. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:5517495–97 [Google Scholar]
  47. Lemke H, Hämmerling GJ, Hohmann C, Rajewsky K. 47.  1978. Hybrid cell lines secreting monoclonal antibody specific for major histocompatibility antigens of the mouse. Nature 271:5642249–51 [Google Scholar]
  48. Hämmerling GJ, Lemke H, Hämmerling U, Höhmann C, Wallich R, Rajewsky K. 48.  1978. Monoclonal antibodies against murine cell surface antigens: anti-H-2, anti-Ia and anti-T cell antibodies. Curr. Top. Microbiol. Immunol. 81:100–6 [Google Scholar]
  49. Kearney JF, Radbruch A, Liesegang B, Rajewsky K. 49.  1979. A new mouse myeloma cell line that has lost immunoglobulin expression but permits the construction of antibody-secreting hybrid cell lines. J. Immunol. 123:41548–50 [Google Scholar]
  50. Reth M, Hämmerling GJ, Rajewsky K. 50.  1978. Analysis of the repertoire of anti-NP antibodies in C57BL/6 mice by cell fusion. I. Characterization of antibody families in the primary and hyperimmune response. Eur. J. Immunol. 8:6393–400 [Google Scholar]
  51. Reth M, Imanishi-Kari T, Rajewsky K. 51.  1979. Analysis of the repertoire of anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) antibodies in C 57 BL/6 mice by cell fusion. II. Characterization of idiotopes by monoclonal anti-idiotope antibodies. Eur. J. Immunol. 9:121004–13 [Google Scholar]
  52. Sablitzky F, Rajewsky K. 52.  1984. Molecular basis of an isogeneic anti-idiotypic response. EMBO J. 3:123005–12 [Google Scholar]
  53. Bothwell AL, Paskind M, Reth M, Imanishi-Kari T, Rajewsky K, Baltimore D. 53.  1981. Heavy chain variable region contribution to the NPb family of antibodies: somatic mutation evident in a γ2a variable region. Cell 24:3625–37 [Google Scholar]
  54. Bothwell AL, Paskind M, Reth M, Imanishi-Kari T, Rajewsky K, Baltimore D. 54.  1982. Somatic variants of murine immunoglobulin λ light chains. Nature 298:5872380–82 [Google Scholar]
  55. Kelsoe G, Reth M, Rajewsky K. 55.  1980. Control of idiotope expression by monoclonal anti-idiotope antibodies. Immunol. Rev. 52:75–88 [Google Scholar]
  56. Rajewsky K, Takemori T. 56.  1983. Genetics, expression, and function of idiotypes. Annu. Rev. Immunol. 1:569–607 [Google Scholar]
  57. Tokuhisa T, Rajewsky K. 57.  1985. Antigen induces chronic idiotype suppression. Proc. Natl. Acad. Sci. USA 82:124217–20 [Google Scholar]
  58. Saito T, Tokuhisa T, Rajewsky K. 58.  1986. Induction of chronic idiotype suppression by ligands binding to the variable (not the constant) region of the idiotypic target. Eur. J. Immunol. 16:111419–25 [Google Scholar]
  59. Potter M. 59.  1977. Antigen-binding myeloma proteins of mice. Adv. Immunol. 25:141–211 [Google Scholar]
  60. Radbruch A, Liesegang B, Rajewsky K. 60.  1980. Isolation of variants of mouse myeloma X63 that express changed immunoglobulin class. Proc. Natl. Acad. Sci. USA 77:52909–13 [Google Scholar]
  61. Weigert MG, Cesari IM, Yonkovich SJ, Cohn M. 61.  1970. Variability in the λ light chain sequences of mouse antibody. Nature 228:52761045–47 [Google Scholar]
  62. Holtkamp B, Cramer M, Lemke H, Rajewsky K. 62.  1981. Isolation of a cloned cell line expressing variant H-2Kk using fluorescence-activated cell sorting. Nature 289:579366–68 [Google Scholar]
  63. Neuberger MS, Rajewsky K. 63.  1981. Switch from hapten-specific immunoglobulin M to immunoglobulin D secretion in a hybrid mouse cell line. Proc. Natl. Acad. Sci. USA 78:21138–42 [Google Scholar]
  64. Neuberger MS, Rajewsky K. 64.  1981. Activation of mouse complement by monoclonal mouse antibodies. Eur. J. Immunol. 11:121012–16 [Google Scholar]
  65. Brüggemann M, Radbruch A, Rajewsky K. 65.  1982. Immunoglobulin V region variants in hybridoma cells. I. Isolation of a variant with altered idiotypic and antigen binding specificity. EMBO J. 1:5629–34 [Google Scholar]
  66. Dildrop R, Brüggemann M, Radbruch A, Rajewsky K, Beyreuther K. 66.  1982. Immunoglobulin V region variants in hybridoma cells. II. Recombination between V genes. EMBO J. 1:5635–40 [Google Scholar]
  67. Radbruch A, Zaiss S, Kappen C, Brüggemann M, Beyreuther K, Rajewsky K. 67.  1985. Drastic change in idiotypic but not antigen-binding specificity of an antibody by a single amino-acid substitution. Nature 315:6019506–8 [Google Scholar]
  68. Reynaud CA, Anquez V, Dahan A, Weill JC. 68.  1985. A single rearrangement event generates most of the chicken immunoglobulin light chain diversity. Cell 40:2283–91 [Google Scholar]
  69. Radbruch A, Müller W, Rajewsky K. 69.  1986. Class switch recombination is IgG1 specific on active and inactive IgH loci of IgG1-secreting B-cell blasts. Proc. Natl. Acad. Sci. USA 83:113954–57 [Google Scholar]
  70. Gearhart PJ, Johnson ND, Douglas R, Hood L. 70.  1981. IgG antibodies to phosphorylcholine exhibit more diversity than their IgM counterparts. Nature 291:581029–34 [Google Scholar]
  71. Cumano A, Rajewsky K. 71.  1985. Structure of primary anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) antibodies in normal and idiotypically suppressed C57BL/6 mice. Eur. J. Immunol. 15:5512–20 [Google Scholar]
  72. Cumano A, Rajewsky K. 72.  1986. Clonal recruitment and somatic mutation in the generation of immunological memory to the hapten NP. EMBO J. 5:102459–68 [Google Scholar]
  73. Allen D. 73.  et al. 1988. Antibody engineering for the analysis of affinity maturation of an anti-hapten response. EMBO J. 7:71995–2001 [Google Scholar]
  74. Förster I, Rajewsky K. 74.  1987. Expansion and functional activity of Ly-1+ B cells upon transfer of peritoneal cells into allotype-congenic, newborn mice. Eur. J. Immunol. 17:4521–28 [Google Scholar]
  75. Förster I, Gu H, Rajewsky K. 75.  1988. Germline antibody V regions as determinants of clonal persistence and malignant growth in the B cell compartment. EMBO J. 7:123693–703 [Google Scholar]
  76. Gu H, Förster I, Rajewsky K. 76.  1990. Sequence homologies, N sequence insertion and JH gene utilization in VHDJH joining: implications for the joining mechanism and the ontogenetic timing of Ly1 B cell and B-CLL progenitor generation. EMBO J. 9:72133–40 [Google Scholar]
  77. Gu H, Kitamura D, Rajewsky K. 77.  1991. B cell development regulated by gene rearrangement: arrest of maturation by membrane-bound D μ protein and selection of DH element reading frames. Cell 65:147–54 [Google Scholar]
  78. Tarlinton D, Förster I, Rajewsky K. 78.  1992. An explanation for the defect in secretion of IgM Mott cells and their predominant occurrence in the Ly-1 B cell compartment. Eur. J. Immunol. 22:2531–39 [Google Scholar]
  79. Rajewsky K, Förster I, Cumano A. 79.  1987. Evolutionary and somatic selection of the antibody repertoire in the mouse. Science 238:48301088–94 [Google Scholar]
  80. McKean D, Huppi K, Bell M, Staudt L, Gerhard W, Weigert M. 80.  1984. Generation of antibody diversity in the immune response of BALB/c mice to influenza virus hemagglutinin. Proc. Natl. Acad. Sci. USA 81:103180–84 [Google Scholar]
  81. Rudikoff S, Pawlita M, Pumphrey J, Heller M. 81.  1984. Somatic diversification of immunoglobulins. Proc. Natl. Acad. Sci. USA 81:72162–66 [Google Scholar]
  82. Sablitzky F, Wildner G, Rajewsky K. 82.  1985. Somatic mutation and clonal expansion of B cells in an antigen-driven immune response. EMBO J. 4:2345–50 [Google Scholar]
  83. Kocks C, Rajewsky K. 83.  1988. Stepwise intraclonal maturation of antibody affinity through somatic hypermutation. Proc. Natl. Acad. Sci. USA 85:218206–10 [Google Scholar]
  84. Dildrop R. 84.  1984. A new classification of mouse VH sequences. Immunol. Today 5:485–86 [Google Scholar]
  85. Timofeeff-Ressovsky NW, Zimmer KG, Delbrück M. 85.  1935. Über die Natur der Genmutation und der Genstruktur, Nachrichten von der Gesellschaft der Wissenschaften zu Göttingen. Biologie 1:189–245 [Google Scholar]
  86. Siekevitz M, Kocks C, Rajewsky K, Dildrop R. 86.  1987. Analysis of somatic mutation and class switching in naive and memory B cells generating adoptive primary and secondary responses. Cell 48:5757–70 [Google Scholar]
  87. Kocks C, Rajewsky K. 87.  1989. Stable expression and somatic hypermutation of antibody V regions in B-cell developmental pathways. Annu. Rev. Immunol. 7:537–59 [Google Scholar]
  88. Hayakawa K, Ishii R, Yamasaki K, Kishimoto T, Hardy RR. 88.  1987. Isolation of high-affinity memory B cells: phycoerythrin as a probe for antigen-binding cells. Proc. Natl. Acad. Sci. USA 84:51379–83 [Google Scholar]
  89. Schittek B, Rajewsky K. 89.  1990. Maintenance of B-cell memory by long-lived cells generated from proliferating precursors. Nature 346:6286749–51 [Google Scholar]
  90. Förster I, Vieira P, Rajewsky K. 90.  1989. Flow cytometric analysis of cell proliferation dynamics in the B cell compartment of the mouse. Int. Immunol. 1:4321–31 [Google Scholar]
  91. Förster I, Rajewsky K. 91.  1990. The bulk of the peripheral B-cell pool in mice is stable and not rapidly renewed from the bone marrow. Proc. Natl. Acad. Sci. USA 87:124781–84 [Google Scholar]
  92. Weiss U, Rajewsky K. 92.  1990. The repertoire of somatic antibody mutants accumulating in the memory compartment after primary immunization is restricted through affinity maturation and mirrors that expressed in the secondary response. J. Exp. Med. 172:61681–89 [Google Scholar]
  93. MacLennan I. 93.  1991. Immunology. The centre of hypermutation. Nature 354:6352352–53 [Google Scholar]
  94. Jacob J, Kelsoe G, Rajewsky K, Weiss U. 94.  1991. Intraclonal generation of antibody mutants in germinal centres. Nature 354:6352389–92 [Google Scholar]
  95. Berek C, Berger A, Apel M. 95.  1991. Maturation of the immune response in germinal centers. Cell 67:61121–29 [Google Scholar]
  96. Ehlich A, Schaal S, Gu H, Kitamura D, Müller W, Rajewsky K. 96.  1993. Immunoglobulin heavy and light chain genes rearrange independently at early stages of B cell development. Cell 72:5695–704 [Google Scholar]
  97. Ehlich A, Martin V, Müller W, Rajewsky K. 97.  1994. Analysis of the B-cell progenitor compartment at the level of single cells. Curr. Biol. 4:7573–83 [Google Scholar]
  98. Löffert D, Ehlich A, Müller W, Rajewsky K. 98.  1996. Surrogate light chain expression is required to establish immunoglobulin heavy chain allelic exclusion during early B cell development. Immunity 4:2133–44 [Google Scholar]
  99. Novobrantseva TI, Martin VM, Pelanda R, Müller W, Rajewsky K, Ehlich A. 99.  1999. Rearrangement and expression of immunoglobulin light chain genes can precede heavy chain expression during normal B cell development in mice. J. Exp. Med. 189:175–88 [Google Scholar]
  100. Bräuninger A, Goossens T, Rajewsky K, Küppers R. 100.  2001. Regulation of immunoglobulin light chain gene rearrangements during early B cell development in the human. Eur. J. Immunol. 31:123631–37 [Google Scholar]
  101. Goossens T, Bräuninger A, Klein U, Küppers R, Rajewsky K. 101.  2001. Receptor revision plays no major role in shaping the receptor repertoire of human memory B cells after the onset of somatic hypermutation. Eur. J. Immunol. 31:123638–48 [Google Scholar]
  102. Küppers R, Zhao M, Hansmann ML, Rajewsky K. 102.  1993. Tracing B cell development in human germinal centres by molecular analysis of single cells picked from histological sections. EMBO J. 12:134955–67 [Google Scholar]
  103. Klein U, Küppers R, Rajewsky K. 103.  1997. Evidence for a large compartment of IgM-expressing memory B cells in humans. Blood 89:41288–98 [Google Scholar]
  104. Stevenson F, Sahota S, Zhu D, Ottensmeier C, Chapman C, Oscier D, Hamblin T. 104.  1998. Insight into the origin and clonal history of B-cell tumors as revealed by analysis of immunoglobulin variable region genes. Immunol. Rev. 162:247–59 [Google Scholar]
  105. Küppers R, Klein U, Hansmann ML, Rajewsky K. 105.  1999. Cellular origin of human B-cell lymphomas. N. Engl. J. Med. 341:201520–29 [Google Scholar]
  106. Hodgkin T. 106.  1832. On some morbid experiences of the absorbent glands and spleen. Med. Chir. Trans. 17:69–97 [Google Scholar]
  107. Sternberg C. 107.  1898. Über eine eigenartige unter dem Bilde der Pseudoleukämie verlaufende Tuberkulose des lymphatischen Apparates. Z. Heilkunde 19:21–90 [Google Scholar]
  108. Reed D. 108.  1902. On the pathological changes in Hodgkin's disease, with special reference to its relationship to tuberculosis. J. Hopkins Hosp. Rep. 10:133–96 [Google Scholar]
  109. Küppers R, Rajewsky K, Zhao M, Simons G, Laumann R. 109.  et al. 1994. Hodgkin disease: Hodgkin and Reed-Sternberg cells picked from histological sections show clonal immunoglobulin gene rearrangements and appear to be derived from B cells at various stages of development. Proc. Natl. Acad. Sci. USA 91:2310962–66 [Google Scholar]
  110. Kanzler H, Küppers R, Hansmann ML, Rajewsky K. 110.  1996. Hodgkin and Reed-Sternberg cells in Hodgkin's disease represent the outgrowth of a dominant tumor clone derived from (crippled) germinal center B cells. J. Exp. Med. 184:41495–505 [Google Scholar]
  111. Küppers R, Rajewsky K. 111.  1998. The origin of Hodgkin and Reed/Sternberg cells in Hodgkin's disease. Annu. Rev. Immunol. 16:471–93 [Google Scholar]
  112. Müschen M, Rajewsky K, Bräuninger A, Baur AS, Oudejans JJ. 112.  et al. 2000. Rare occurrence of classical Hodgkin's disease as a T cell lymphoma. J. Exp. Med. 191:2387–94 [Google Scholar]
  113. Seitz V, Hummel M, Marafioti T, Anagnostopoulos I, Assaf C, Stein H. 113.  2000. Detection of clonal T-cell receptor γ-chain gene rearrangements in Reed-Sternberg cells of classic Hodgkin disease. Blood 95:103020–24 [Google Scholar]
  114. Ohno T, Smir BN, Weisenburger DD, Gascoyne RD, Hinrichs SD, Chan WC. 114.  1998. Origin of the Hodgkin/Reed-Sternberg cells in chronic lymphocytic leukemia with “Hodgkin's transformation.”. Blood 91:51757–61 [Google Scholar]
  115. Bräuninger A, Hansmann ML, Strickler JG, Dummer R, Burg G. 115.  et al. 1999. Identification of common germinal-center B-cell precursors in two patients with both Hodgkin's disease and non-Hodgkin's lymphoma. N. Engl. J. Med. 340:161239–47 [Google Scholar]
  116. Marafioti T, Hummel M, Anagnostopoulos I, Foss HD, Huhn D, Stein H. 116.  1999. Classical Hodgkin's disease and follicular lymphoma originating from the same germinal center B cell. J. Clin. Oncol. 17:123804–9 [Google Scholar]
  117. Kanzler H, Küppers R, Helmes S, Wacker HH, Chott A. 117.  et al. 2000. Hodgkin and Reed-Sternberg-like cells in B-cell chronic lymphocytic leukemia represent the outgrowth of single germinal-center B-cell-derived clones: potential precursors of Hodgkin and Reed-Sternberg cells in Hodgkin's disease. Blood 95:31023–31 [Google Scholar]
  118. Küppers R, Sousa AB, Baur AS, Strickler JG, Rajewsky K, Hansmann ML. 118.  2001. Common germinal-center B-cell origin of the malignant cells in two composite lymphomas, involving classical Hodgkin's disease and either follicular lymphoma or B-CLL. Mol. Med. 7:5285–92 [Google Scholar]
  119. Thomas KR, Capecchi MR. 119.  1987. Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell 51:3503–12 [Google Scholar]
  120. Kitamura D, Roes J, Kühn R, Rajewsky K. 120.  1991. A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin μ chain gene. Nature 350:6317423–26 [Google Scholar]
  121. Kitamura D, Rajewsky K. 121.  1992. Targeted disruption of μ chain membrane exon causes loss of heavy-chain allelic exclusion. Nature 356:6365154–56 [Google Scholar]
  122. Kitamura D, Kudo A, Schaal S, Müller W, Melchers F, Rajewsky K. 122.  1992. A critical role of λ 5 protein in B cell development. Cell 69:5823–31 [Google Scholar]
  123. Kühn R, Rajewsky K, Müller W. 123.  1991. Generation and analysis of interleukin-4 deficient mice. Science 254:5032707–10 [Google Scholar]
  124. Kühn R, Löhler J, Rennick D, Rajewsky K, Müller W. 124.  1993. Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75:2263–74 [Google Scholar]
  125. Roes J, Rajewsky K. 125.  1993. Immunoglobulin D (IgD)-deficient mice reveal an auxiliary receptor function for IgD in antigen-mediated recruitment of B cells. J. Exp. Med. 177:145–55 [Google Scholar]
  126. Roes J, Rajewsky K. 126.  1991. Cell autonomous expression of IgD is not essential for the maturation of conventional B cells. Int. Immunol. 3:121367–71 [Google Scholar]
  127. Chen J, Lansford R, Stewart V, Young F, Alt FW. 127.  1993. RAG-2-deficient blastocyst complementation: an assay of gene function in lymphocyte development. Proc. Natl. Acad. Sci. USA 90:104528–32 [Google Scholar]
  128. Tarakhovsky A, Müller W, Rajewsky K. 128.  1994. Lymphocyte populations and immune responses in CD5-deficient mice. Eur. J. Immunol. 24:71678–84 [Google Scholar]
  129. Tarakhovsky A, Kanner SB, Hombach J, Ledbetter JA, Müller W. 129.  et al. 1995. A role for CD5 in TCR-mediated signal transduction and thymocyte selection. Science 269:5223535–37 [Google Scholar]
  130. Tarakhovsky A, Turner M, Schaal S, Mee PJ, Duddy LP. 130.  et al. 1995. Defective antigen receptor-mediated proliferation of B and T cells in the absence of Vav. Nature 374:6521467–70 [Google Scholar]
  131. Fehling HJ, Swat W, Laplace C, Kühn R, Rajewsky K. 131.  et al. 1994. MHC class I expression in mice lacking the proteasome subunit LMP-7. Science 265:51761234–37 [Google Scholar]
  132. DiSanto JP, Müller W, Guy-Grand D, Fischer A, Rajewsky K. 132.  1995. Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor γ chain. Proc. Natl. Acad. Sci. USA 92:2377–81 [Google Scholar]
  133. Taki S, Meiering M, Rajewsky K. 133.  1993. Targeted insertion of a variable region gene into the immunoglobulin heavy chain locus. Science 262:51371268–71 [Google Scholar]
  134. Taki S, Schwenk F, Rajewsky K. 134.  1995. Rearrangement of upstream DH and VH genes to a rearranged immunoglobulin variable region gene inserted into the DQ52-JH region of the immunoglobulin heavy chain locus. Eur. J. Immunol. 25:71888–96 [Google Scholar]
  135. Zou YR, Gu H, Rajewsky K. 135.  1993. Generation of a mouse strain that produces immunoglobulin κ chains with human constant regions. Science 262:51371271–74 [Google Scholar]
  136. Sauer B, Henderson N. 136.  1988. Site-specific DNA recombination in mammalian cells by the Cre recombinase of bacteriophage P1. Proc. Natl. Acad. Sci. USA 85:145166–70 [Google Scholar]
  137. O'Gorman S, Fox DT, Wahl GM. 137.  1991. Recombinase-mediated gene activation and site-specific integration in mammalian cells. Science 251:49991351–55 [Google Scholar]
  138. Jung S, Rajewsky K, Radbruch A. 138.  1993. Shutdown of class switch recombination by deletion of a switch region control element. Science 259:5097984–87 [Google Scholar]
  139. Rodriguez CI, Buchholz F, Galloway J, Sequerra R, Kasper J. 139.  et al. 2000. High-efficiency deleter mice show that FLPe is an alternative to Cre-loxP. Nat. Genet. 25:2139–40 [Google Scholar]
  140. Gu H, Zou YR, Rajewsky K. 140.  1993. Independent control of immunoglobulin switch recombination at individual switch regions evidenced through Cre-loxP-mediated gene targeting. Cell 73:61155–64 [Google Scholar]
  141. Esposito G, Texido G, Betz UA, Gu H, Müller W. 141.  et al. 2000. Mice reconstituted with DNA polymerase β-deficient fetal liver cells are able to mount a T cell-dependent immune response and mutate their Ig genes normally. Proc. Natl. Acad. Sci. USA 97:31166–71 [Google Scholar]
  142. Lakso M, Sauer B, Mosinger B Jr, Lee EJ, Manning RW. 142.  et al. 1992. Targeted oncogene activation by site-specific recombination in transgenic mice. Proc. Natl. Acad. Sci. USA 89:146232–36 [Google Scholar]
  143. Orban PC, Chui D, Marth JD. 143.  1992. Tissue- and site-specific DNA recombination in transgenic mice. Proc. Natl. Acad. Sci. USA 89:156861–65 [Google Scholar]
  144. Gu H, Marth JD, Orban PC, Mossmann H, Rajewsky K. 144.  1994. Deletion of a DNA polymerase β gene segment in T cells using cell type-specific gene targeting. Science 265:5168103–6 [Google Scholar]
  145. Rajewsky K, Gu H, Kühn R, Betz UA, Müller W. 145.  et al. 1996. Conditional gene targeting. J. Clin. Invest. 98:3600–3 [Google Scholar]
  146. Gossen M, Bujard H. 146.  1992. Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc. Natl. Acad. Sci. USA 89:125547–51 [Google Scholar]
  147. Zou YR, Müller W, Gu H, Rajewsky K. 147.  1994. Cre-loxP-mediated gene replacement: a mouse strain producing humanized antibodies. Curr. Biol. 4:121099–103 [Google Scholar]
  148. Kühn R, Schwenk F, Aguet M, Rajewsky K. 148.  1995. Inducible gene targeting in mice. Science 269:52291427–29 [Google Scholar]
  149. Schwenk F, Kuhn R, Angrand PO, Rajewsky K, Stewart AF. 149.  1998. Temporally and spatially regulated somatic mutagenesis in mice. Nucleic Acids Res. 26:61427–32 [Google Scholar]
  150. Maruyama M, Lam KP, Rajewsky K. 150.  2000. Memory B-cell persistence is independent of persisting immunizing antigen. Nature 407:6804636–42 [Google Scholar]
  151. Rickert RC, Rajewsky K, Roes J. 151.  1995. Impairment of T-cell-dependent B-cell responses and B-1 cell development in CD19-deficient mice. Nature 376:6538352–55 [Google Scholar]
  152. Rickert RC, Roes J, Rajewsky K. 152.  1997. B lymphocyte-specific, Cre-mediated mutagenesis in mice. Nucleic Acids Res. 25:61317–18 [Google Scholar]
  153. Rajewsky K. 153.  1996. Clonal selection and learning in the antibody system. Nature 381:6585751–58 [Google Scholar]
  154. Zou YR, Takeda S, Rajewsky K. 154.  1993. Gene targeting in the Igκ locus: efficient generation of λ chain-expressing B cells, independent of gene rearrangements in Igκ.. EMBO J. 12:3811–20 [Google Scholar]
  155. Chen J, Trounstine M, Kurahara C, Young F, Kuo CC. 155.  et al. 1993. B cell development in mice that lack one or both immunoglobulin κ light chain genes. EMBO J. 12:3821–30 [Google Scholar]
  156. Takeda S, Zou YR, Bluethmann H, Kitamura D, Muller U, Rajewsky K. 156.  1993. Deletion of the immunoglobulin κ chain intron enhancer abolishes κ chain gene rearrangement in cis but not λ chain gene rearrangement in trans. EMBO J. 12:62329–36 [Google Scholar]
  157. Sonoda E, Pewzner-Jung Y, Schwers S, Taki S, Jung S. 157.  et al. 1997. B cell development under the condition of allelic inclusion. Immunity 6:3225–33 [Google Scholar]
  158. Wabl M, Steinberg C. 158.  1982. A theory of allelic and isotypic exclusion for immunoglobulin genes. Proc. Natl. Acad. Sci. USA 79:226976–78 [Google Scholar]
  159. Polic B, Kunkel D, Scheffold A, Rajewsky K. 159.  2001. How αβ T cells deal with induced TCRα ablation. Proc. Natl. Acad. Sci. USA 98:158744–49 [Google Scholar]
  160. Lam KP, Kühn R, Rajewsky K. 160.  1997. In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid cell death. Cell 90:61073–83 [Google Scholar]
  161. Kraus M, Alimzhanov MB, Rajewsky N, Rajewsky K. 161.  2004. Survival of resting mature B lymphocytes depends on BCR signaling via the Igα/β heterodimer. Cell 117:6787–800 [Google Scholar]
  162. Srinivasan L, Sasaki Y, Calado DP, Zhang B, Paik JH. 162.  et al. 2009. PI3 kinase signals BCR-dependent mature B cell survival. Cell 139:3573–86 [Google Scholar]
  163. Ferradini L, Gu H, De Smet A, Rajewsky K, Reynaud CA, Weill JC. 163.  1996. Rearrangement-enhancing element upstream of the mouse immunoglobulin κ chain J cluster. Science 271:52541416–20 [Google Scholar]
  164. Pelanda R, Schaal S, Torres RM, Rajewsky K. 164.  1996. A prematurely expressed Igκ transgene, but not VκJκ gene segment targeted into the Igκ locus, can rescue B cell development in λ5-deficient mice. Immunity 5:3229–39 [Google Scholar]
  165. Pelanda R, Schwers S, Sonoda E, Torres RM, Nemazee D, Rajewsky K. 165.  1997. Receptor editing in a transgenic mouse model: site, efficiency, and role in B cell tolerance and antibody diversification. Immunity 7:6765–75 [Google Scholar]
  166. Pewzner-Jung Y, Friedmann D, Sonoda E, Jung S, Rajewsky K, Eilat D. 166.  1998. B cell deletion, anergy, and receptor editing in “knock in” mice targeted with a germline-encoded or somatically mutated anti-DNA heavy chain. J. Immunol. 161:94634–45 [Google Scholar]
  167. Buch T, Rieux-Laucat F, Förster I, Rajewsky K. 167.  2002. Failure of HY-specific thymocytes to escape negative selection by receptor editing. Immunity 16:5707–18 [Google Scholar]
  168. Torres RM, Flaswinkel H, Reth M, Rajewsky K. 168.  1996. Aberrant B cell development and immune response in mice with a compromised BCR complex. Science 272:52691804–8 [Google Scholar]
  169. Kaisho T, Schwenk F, Rajewsky K. 169.  1997. The roles of γ1 heavy chain membrane expression and cytoplasmic tail in IgG1 responses. Science 276:5311412–15 [Google Scholar]
  170. Kraus M, Saijo K, Torres RM, Rajewsky K. 170.  1999. Ig-α cytoplasmic truncation renders immature B cells more sensitive to antigen contact. Immunity 11:5537–45 [Google Scholar]
  171. Fukita Y, Jacobs H, Rajewsky K. 171.  1998. Somatic hypermutation in the heavy chain locus correlates with transcription. Immunity 9:1105–14 [Google Scholar]
  172. Jacobs H, Fukita Y, van der Horst GT, de Boer J, Weeda G. 172.  et al. 1998. Hypermutation of immunoglobulin genes in memory B cells of DNA repair-deficient mice. J. Exp. Med. 187:111735–43 [Google Scholar]
  173. Esposito G, Texido G, Betz UAK, Gu H, Müller W. 173.  et al. 2000. Mice reconstituted with DNA polymerase β-deficient fetal liver cells are able to mount a T cell–dependent immune response and mutate their Ig genes normally. Proc. Natl. Acad. Sci. USA 97:31166–71 [Google Scholar]
  174. Hao Z, Rajewsky K. 174.  2001. Homeostasis of peripheral B cells in the absence of B cell influx from the bone marrow. J. Exp. Med. 194:81151–64 [Google Scholar]
  175. Wagner N, Löhler J, Kunkel EJ, Ley K, Leung E. 175.  et al. 1996. Critical role for β7 integrins in formation of the gut-associated lymphoid tissue. Nature 382:6589366–70 [Google Scholar]
  176. Betz UA, Bloch W, van den Broek M, Yoshida K, Taga T. 176.  et al. 1998. Postnatally induced inactivation of gp130 in mice results in neurological, cardiac, hematopoietic, immunological, hepatic, and pulmonary defects. J. Exp. Med. 188:101955–65 [Google Scholar]
  177. Hirota H, Chen J, Betz UA, Rajewsky K, Gu Y. 177.  et al. 1999. Loss of a gp130 cardiac muscle cell survival pathway is a critical event in the onset of heart failure during biomechanical stress. Cell 97:2189–98 [Google Scholar]
  178. Schmidt-Supprian M, Bloch W, Courtois G, Addicks K, Israël A. 178.  et al. 2000. NEMO/IKKγ-deficient mice model incontinentia pigmenti. Mol. Cell 5:6981–92 [Google Scholar]
  179. Zhang B, Kracker S, Yasuda T, Casola S, Vanneman M. 179.  et al. 2012. Immune surveillance and therapy of lymphomas driven by Epstein-Barr-virus protein LMP1 in a mouse model. Cell 148:3739–51 [Google Scholar]
/content/journals/10.1146/annurev.immunol.021908.132646
Loading

Supplementary Data

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error