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. 1994 Jul;97(Suppl 1):3–9.

B lymphocyte ontogeny and immunoglobulin production.

F Hentges 1
PMCID: PMC1550373  PMID: 8033431

Abstract

In this paper we review different aspects of B cell development on the path from the proB cell to the memory B cell and the plasmocyte. Emphasis is given to the positive and negative selection effects mediated by the changing forms of the surface immunoglobulin (Ig) receptor under successive microenvironments. Positive selection is linked to lambda chain expression at the pro- and preB cell stage in fetal liver and bone marrow. Negative selection takes place when surface (s)IgM is being cross-linked by autoantigens before the immature B cell can leave, or after it has left, the bone marrow. After somatic mutation, major expansion becomes possible for B cells with high-affinity sIg receptors. This takes place in the germinal centres of the secondary lymphoid organs in the context of major histocompatibility complex (MHC) restriction and provided the necessary T cell help is given. Kinetic data on B cell replenishment in the rodent models are used to draw a schematic view of an established B cell repertoire.

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Selected References

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  1. Bazin H., Platteau B., Maclennan I. C., Johnson G. D. B-cell production and differentiation in adult rats. Immunology. 1985 Jan;54(1):79–88. [PMC free article] [PubMed] [Google Scholar]
  2. Benner R., Hijmans W., Haaijman J. J. The bone marrow: the major source of serum immunoglobulins, but still a neglected site of antibody formation. Clin Exp Immunol. 1981 Oct;46(1):1–8. [PMC free article] [PubMed] [Google Scholar]
  3. Benner R., Meima F., van der Meulen G. M., van Muiswinkel W. B. Antibody formation in mouse bone marrow. I. Evidence for the development of plaque-forming cells in situ. Immunology. 1974 Feb;26(2):247–255. [PMC free article] [PubMed] [Google Scholar]
  4. Berek C., Milstein C. Mutation drift and repertoire shift in the maturation of the immune response. Immunol Rev. 1987 Apr;96:23–41. doi: 10.1111/j.1600-065x.1987.tb00507.x. [DOI] [PubMed] [Google Scholar]
  5. Berek C. The development of B cells and the B-cell repertoire in the microenvironment of the germinal center. Immunol Rev. 1992 Apr;126:5–19. doi: 10.1111/j.1600-065x.1992.tb00628.x. [DOI] [PubMed] [Google Scholar]
  6. Brahim F., Osmond D. G. Migration of bone marrow lymphocytes demonstrated by selective bone marrow labeling with thymidine-H3. Anat Rec. 1970 Oct;168(2):139–159. doi: 10.1002/ar.1091680202. [DOI] [PubMed] [Google Scholar]
  7. Brahim F., Osmond D. G. Migration of newly formed small lymphocytes from bone marrow to lymph nodes during primary immune responses. Clin Exp Immunol. 1976 Jun;24(3):516–526. [PMC free article] [PubMed] [Google Scholar]
  8. Brombacher F., Köhler G., Eibel H. B cell tolerance in mice transgenic for anti-CD8 immunoglobulin mu chain. J Exp Med. 1991 Dec 1;174(6):1335–1346. doi: 10.1084/jem.174.6.1335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Clark E. A., Ledbetter J. A. Activation of human B cells mediated through two distinct cell surface differentiation antigens, Bp35 and Bp50. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4494–4498. doi: 10.1073/pnas.83.12.4494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Coico R. F., Bhogal B. S., Thorbecke G. J. Relationship of germinal centers in lymphoid tissue to immunologic memory. VI. Transfer of B cell memory with lymph node cells fractionated according to their receptors for peanut agglutinin. J Immunol. 1983 Nov;131(5):2254–2257. [PubMed] [Google Scholar]
  11. Dilosa R. M., Maeda K., Masuda A., Szakal A. K., Tew J. G. Germinal center B cells and antibody production in the bone marrow. J Immunol. 1991 Jun 15;146(12):4071–4077. [PubMed] [Google Scholar]
  12. FLIEDNER T., KESSE M., CRONKITE E. P., ROBERTSON J. S. CELL PROLIFERATION IN GERMINAL CENTERS OF THE RAT SPLEEN. Ann N Y Acad Sci. 1964 Feb 28;113:578–594. doi: 10.1111/j.1749-6632.1964.tb40692.x. [DOI] [PubMed] [Google Scholar]
  13. Gay D., Saunders T., Camper S., Weigert M. Receptor editing: an approach by autoreactive B cells to escape tolerance. J Exp Med. 1993 Apr 1;177(4):999–1008. doi: 10.1084/jem.177.4.999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gray D., MacLennan I. C., Lane P. J. Virgin B cell recruitment and the lifespan of memory clones during antibody responses to 2,4-dinitrophenyl-hemocyanin. Eur J Immunol. 1986 Jun;16(6):641–648. doi: 10.1002/eji.1830160609. [DOI] [PubMed] [Google Scholar]
  15. Henderson S., Rowe M., Gregory C., Croom-Carter D., Wang F., Longnecker R., Kieff E., Rickinson A. Induction of bcl-2 expression by Epstein-Barr virus latent membrane protein 1 protects infected B cells from programmed cell death. Cell. 1991 Jun 28;65(7):1107–1115. doi: 10.1016/0092-8674(91)90007-l. [DOI] [PubMed] [Google Scholar]
  16. Hirayama F., Shih J. P., Awgulewitsch A., Warr G. W., Clark S. C., Ogawa M. Clonal proliferation of murine lymphohemopoietic progenitors in culture. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5907–5911. doi: 10.1073/pnas.89.13.5907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ho F., Lortan J. E., MacLennan I. C., Khan M. Distinct short-lived and long-lived antibody-producing cell populations. Eur J Immunol. 1986 Oct;16(10):1297–1301. doi: 10.1002/eji.1830161018. [DOI] [PubMed] [Google Scholar]
  18. Hockenbery D., Nuñez G., Milliman C., Schreiber R. D., Korsmeyer S. J. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature. 1990 Nov 22;348(6299):334–336. doi: 10.1038/348334a0. [DOI] [PubMed] [Google Scholar]
  19. Holder M. J., Liu Y. J., Defrance T., Flores-Romo L., MacLennan I. C., Gordon J. Growth factor requirements for the stimulation of germinal center B cells: evidence for an IL-2-dependent pathway of development. Int Immunol. 1991 Dec;3(12):1243–1251. doi: 10.1093/intimm/3.12.1243. [DOI] [PubMed] [Google Scholar]
  20. Jacob J., Kassir R., Kelsoe G. In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. I. The architecture and dynamics of responding cell populations. J Exp Med. 1991 May 1;173(5):1165–1175. doi: 10.1084/jem.173.5.1165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kitamura D., Kudo A., Schaal S., Müller W., Melchers F., Rajewsky K. A critical role of lambda 5 protein in B cell development. Cell. 1992 May 29;69(5):823–831. doi: 10.1016/0092-8674(92)90293-l. [DOI] [PubMed] [Google Scholar]
  22. Kosco M. H., Burton G. F., Kapasi Z. F., Szakal A. K., Tew J. G. Antibody-forming cell induction during an early phase of germinal centre development and its delay with ageing. Immunology. 1989 Nov;68(3):312–318. [PMC free article] [PubMed] [Google Scholar]
  23. Kosco M. H., Gray D. Signals involved in germinal center reactions. Immunol Rev. 1992 Apr;126:63–76. doi: 10.1111/j.1600-065x.1992.tb00631.x. [DOI] [PubMed] [Google Scholar]
  24. Kraal G., Weissman I. L., Butcher E. C. Memory B cells express a phenotype consistent with migratory competence after secondary but not short-term primary immunization. Cell Immunol. 1988 Aug;115(1):78–87. doi: 10.1016/0008-8749(88)90163-3. [DOI] [PubMed] [Google Scholar]
  25. Kroese F. G., Seijen H. G., Nieuwenhuis P. The initiation of germinal centre reactivity. Res Immunol. 1991 Mar-Apr;142(3):249–252. doi: 10.1016/0923-2494(91)90069-u. [DOI] [PubMed] [Google Scholar]
  26. Kroese F. G., Timens W., Nieuwenhuis P. Germinal center reaction and B lymphocytes: morphology and function. Curr Top Pathol. 1990;84(Pt 1):103–148. doi: 10.1007/978-3-642-75519-4_5. [DOI] [PubMed] [Google Scholar]
  27. Landreth K. S., Narayanan R., Dorshkind K. Insulin-like growth factor-I regulates pro-B cell differentiation. Blood. 1992 Sep 1;80(5):1207–1212. [PubMed] [Google Scholar]
  28. Liu Y. J., Cairns J. A., Holder M. J., Abbot S. D., Jansen K. U., Bonnefoy J. Y., Gordon J., MacLennan I. C. Recombinant 25-kDa CD23 and interleukin 1 alpha promote the survival of germinal center B cells: evidence for bifurcation in the development of centrocytes rescued from apoptosis. Eur J Immunol. 1991 May;21(5):1107–1114. doi: 10.1002/eji.1830210504. [DOI] [PubMed] [Google Scholar]
  29. Liu Y. J., Johnson G. D., Gordon J., MacLennan I. C. Germinal centres in T-cell-dependent antibody responses. Immunol Today. 1992 Jan;13(1):17–21. doi: 10.1016/0167-5699(92)90199-H. [DOI] [PubMed] [Google Scholar]
  30. Liu Y. J., Joshua D. E., Williams G. T., Smith C. A., Gordon J., MacLennan I. C. Mechanism of antigen-driven selection in germinal centres. Nature. 1989 Dec 21;342(6252):929–931. doi: 10.1038/342929a0. [DOI] [PubMed] [Google Scholar]
  31. Liu Y. J., Mason D. Y., Johnson G. D., Abbot S., Gregory C. D., Hardie D. L., Gordon J., MacLennan I. C. Germinal center cells express bcl-2 protein after activation by signals which prevent their entry into apoptosis. Eur J Immunol. 1991 Aug;21(8):1905–1910. doi: 10.1002/eji.1830210819. [DOI] [PubMed] [Google Scholar]
  32. Liu Y. J., Oldfield S., MacLennan I. C. Memory B cells in T cell-dependent antibody responses colonize the splenic marginal zones. Eur J Immunol. 1988 Mar;18(3):355–362. doi: 10.1002/eji.1830180306. [DOI] [PubMed] [Google Scholar]
  33. Liu Y. J., Zhang J., Lane P. J., Chan E. Y., MacLennan I. C. Sites of specific B cell activation in primary and secondary responses to T cell-dependent and T cell-independent antigens. Eur J Immunol. 1991 Dec;21(12):2951–2962. doi: 10.1002/eji.1830211209. [DOI] [PubMed] [Google Scholar]
  34. MacLennan I. C., Liu Y. J., Johnson G. D. Maturation and dispersal of B-cell clones during T cell-dependent antibody responses. Immunol Rev. 1992 Apr;126:143–161. doi: 10.1111/j.1600-065x.1992.tb00635.x. [DOI] [PubMed] [Google Scholar]
  35. MacLennan I. C., Liu Y. J., Oldfield S., Zhang J., Lane P. J. The evolution of B-cell clones. Curr Top Microbiol Immunol. 1990;159:37–63. doi: 10.1007/978-3-642-75244-5_3. [DOI] [PubMed] [Google Scholar]
  36. McHeyzer-Williams M. G., McLean M. J., Lalor P. A., Nossal G. J. Antigen-driven B cell differentiation in vivo. J Exp Med. 1993 Jul 1;178(1):295–307. doi: 10.1084/jem.178.1.295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. McNiece I. K., Langley K. E., Zsebo K. M. The role of recombinant stem cell factor in early B cell development. Synergistic interaction with IL-7. J Immunol. 1991 Jun 1;146(11):3785–3790. [PubMed] [Google Scholar]
  38. Melchers F., Karasuyama H., Haasner D., Bauer S., Kudo A., Sakaguchi N., Jameson B., Rolink A. The surrogate light chain in B-cell development. Immunol Today. 1993 Feb;14(2):60–68. doi: 10.1016/0167-5699(93)90060-X. [DOI] [PubMed] [Google Scholar]
  39. Morahan G., Brennan F. E., Bhathal P. S., Allison J., Cox K. O., Miller J. F. Expression in transgenic mice of class I histocompatibility antigens controlled by the metallothionein promoter. Proc Natl Acad Sci U S A. 1989 May;86(10):3782–3786. doi: 10.1073/pnas.86.10.3782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Namen A. E., Lupton S., Hjerrild K., Wignall J., Mochizuki D. Y., Schmierer A., Mosley B., March C. J., Urdal D., Gillis S. Stimulation of B-cell progenitors by cloned murine interleukin-7. Nature. 1988 Jun 9;333(6173):571–573. doi: 10.1038/333571a0. [DOI] [PubMed] [Google Scholar]
  41. Nemazee D. A., Bürki K. Clonal deletion of B lymphocytes in a transgenic mouse bearing anti-MHC class I antibody genes. Nature. 1989 Feb 9;337(6207):562–566. doi: 10.1038/337562a0. [DOI] [PubMed] [Google Scholar]
  42. Nieuwenhuis P., Ford W. L. Comparative migration of B- and T-Lymphocytes in the rat spleen and lymph nodes. Cell Immunol. 1976 May;23(2):254–267. doi: 10.1016/0008-8749(76)90191-x. [DOI] [PubMed] [Google Scholar]
  43. Nossal G. J. B-cell selection and tolerance. Curr Opin Immunol. 1991 Apr;3(2):193–198. doi: 10.1016/0952-7915(91)90049-7. [DOI] [PubMed] [Google Scholar]
  44. Nossal G. J. Cellular mechanisms of immunologic tolerance. Annu Rev Immunol. 1983;1:33–62. doi: 10.1146/annurev.iy.01.040183.000341. [DOI] [PubMed] [Google Scholar]
  45. Oettinger M. A., Schatz D. G., Gorka C., Baltimore D. RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination. Science. 1990 Jun 22;248(4962):1517–1523. doi: 10.1126/science.2360047. [DOI] [PubMed] [Google Scholar]
  46. Osmond D. G. Population dynamics of bone marrow B lymphocytes. Immunol Rev. 1986 Oct;93:103–124. doi: 10.1111/j.1600-065x.1986.tb01504.x. [DOI] [PubMed] [Google Scholar]
  47. Press O. W., Rosse C., Clagett J. The distribution of rapidly and slowly renewed T, B, and "null" lymphocytes in mouse bone marrow, thymus, lymph nodes, and spleen. Cell Immunol. 1977 Sep;33(1):114–124. doi: 10.1016/0008-8749(77)90139-3. [DOI] [PubMed] [Google Scholar]
  48. Rosse C., Press O. W. The differentiation of B and T lymphocytes from precursor cells resident in the bone marrow. Blood Cells. 1978;4(1-2):65–85. [PubMed] [Google Scholar]
  49. Russell D. M., Dembić Z., Morahan G., Miller J. F., Bürki K., Nemazee D. Peripheral deletion of self-reactive B cells. Nature. 1991 Nov 28;354(6351):308–311. doi: 10.1038/354308a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Tew J. G., DiLosa R. M., Burton G. F., Kosco M. H., Kupp L. I., Masuda A., Szakal A. K. Germinal centers and antibody production in bone marrow. Immunol Rev. 1992 Apr;126:99–112. doi: 10.1111/j.1600-065x.1992.tb00633.x. [DOI] [PubMed] [Google Scholar]
  51. Tew J. G., Kosco M. H., Burton G. F., Szakal A. K. Follicular dendritic cells as accessory cells. Immunol Rev. 1990 Oct;117:185–211. doi: 10.1111/j.1600-065x.1990.tb00573.x. [DOI] [PubMed] [Google Scholar]
  52. Tiegs S. L., Russell D. M., Nemazee D. Receptor editing in self-reactive bone marrow B cells. J Exp Med. 1993 Apr 1;177(4):1009–1020. doi: 10.1084/jem.177.4.1009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Yoshida Y., Osmond D. G. Homing of bone marrow lymphoid cells. Localization and fate of newly formed cells in lymphocyte-rich marrow fractions injected into lethally X-irradiated recipients. Transplantation. 1978 May;25(5):246–251. [PubMed] [Google Scholar]
  54. Zhang J., MacLennan I. C., Liu Y. J., Lane P. J. Is rapid proliferation in B centroblasts linked to somatic mutation in memory B cell clones? Immunol Lett. 1988 Aug;18(4):297–299. doi: 10.1016/0165-2478(88)90178-2. [DOI] [PubMed] [Google Scholar]

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