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. 1988 Sep;65(1):73–79.

Recruitment of virgin B cells into an immune response is restricted to activation outside lymphoid follicles.

D Gray 1
PMCID: PMC1385022  PMID: 3263314

Abstract

The site and mechanism of recruitment of short-lived new B cells from the bone marrow into the longer-lived recirculating B-cell pool were studied by using kappa-allotype-distinct congenic rats to construct bone marrow chimeras. Chimeras were immunized with antigen in the form of an antigen-antibody complex that is largely restricted to lymphoid follicles, rapidly localizing to follicular dendritic cells (FDC). This form of antigen, although a potent stimulator of memory B cells, was shown to be a very poor inducer of virgin B-cell responses. This was not due solely to differences in receptor affinity, as complexes in which the hapten epitopes were unmasked also evoked little virgin B-cell response. The inability of virgin B cells to be activated by FDC-bound antigen seems to relate to the fact that they are not part of the recirculating pool and do not migrate through lymphoid follicles; restriction of antigen to a draining lymph node also precluded virgin B-cell activation. The evidence presented suggests that activation of virgin B cells at extrafollicular sites in the spleen (red pulp, marginal zone, outer periarteriolar lymphocytic sheath) is required for both their incorporation into immune responses and into the recirculating pool. These experiments also show that established immune responses are maintained by clones activated soon after immunization and not by continued incorporation of new clones.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andersson J., Melchers F., Galanos C., Lüderitz O. The mitogenic effect of lipopolysaccharide on bone marrow-derived mouse lymphocytes. Lipid A as the mitogenic part of the molecule. J Exp Med. 1973 Apr 1;137(4):943–953. doi: 10.1084/jem.137.4.943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. Caulfield M. J., Shaffer D. Immunoregulation by antigen/antibody complexes. I. Specific immunosuppression induced in vivo with immune complexes formed in antibody excess. J Immunol. 1987 Jun 1;138(11):3680–3683. [PubMed] [Google Scholar]
  5. 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]
  6. Deenen G. J., Hunt S. V., Opstelten D. A stathmokinetic study of B lymphocytopoiesis in rat bone marrow: proliferation of cells containing cytoplasmic mu-chains, terminal deoxynucleotidyl transferase and carrying HIS24 antigen. J Immunol. 1987 Aug 1;139(3):702–710. [PubMed] [Google Scholar]
  7. Dennert G. The mechanism of antibody-induced stimulation and inhibition of the immune response. J Immunol. 1971 Apr;106(4):951–955. [PubMed] [Google Scholar]
  8. Gray D., MacLennan I. C., Bazin H., Khan M. Migrant mu+ delta+ and static mu+ delta- B lymphocyte subsets. Eur J Immunol. 1982 Jul;12(7):564–569. doi: 10.1002/eji.1830120707. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Gray D. Population kinetics of rat peripheral B cells. J Exp Med. 1988 Mar 1;167(3):805–816. doi: 10.1084/jem.167.3.805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Herzenberg L. A., Tokuhisa T., Herzenberg L. A. Carrier-priming leads to hapten-specific suppression. Nature. 1980 Jun 26;285(5767):664–667. doi: 10.1038/285664a0. [DOI] [PubMed] [Google Scholar]
  12. Heyman B., Wigzell H. Immunoregulation by monoclonal sheep erythrocyte-specific IgG antibodies: suppression is correlated to level of antigen binding and not to isotype. J Immunol. 1984 Mar;132(3):1136–1143. [PubMed] [Google Scholar]
  13. Hunt S. V., Fowler M. H. A repopulation assay for B and T lymphocyte stem cells employing radiation chimaeras. Cell Tissue Kinet. 1981 Jul;14(4):445–464. doi: 10.1111/j.1365-2184.1981.tb00551.x. [DOI] [PubMed] [Google Scholar]
  14. Kaartinen M., Griffiths G. M., Markham A. F., Milstein C. mRNA sequences define an unusually restricted IgG response to 2-phenyloxazolone and its early diversification. 1983 Jul 28-Aug 3Nature. 304(5924):320–324. doi: 10.1038/304320a0. [DOI] [PubMed] [Google Scholar]
  15. Kaartinen M., Pelkonen J., Mäkelä O. Several V genes participate in the early phenyloxazolone response in various combinations. Eur J Immunol. 1986 Jan;16(1):98–105. doi: 10.1002/eji.1830160119. [DOI] [PubMed] [Google Scholar]
  16. Klaus G. G., Humphrey J. H., Kunkl A., Dongworth D. W. The follicular dendritic cell: its role in antigen presentation in the generation of immunological memory. Immunol Rev. 1980;53:3–28. doi: 10.1111/j.1600-065x.1980.tb01038.x. [DOI] [PubMed] [Google Scholar]
  17. Klaus G. G. The generation of memory cells. II. Generation of B memory cells with preformed antigen-antibody complexes. Immunology. 1978 Apr;34(4):643–652. [PMC free article] [PubMed] [Google Scholar]
  18. Lane P. J., Gray D., Oldfield S., MacLennan I. C. Differences in the recruitment of virgin B cells into antibody responses to thymus-dependent and thymus-independent type-2 antigens. Eur J Immunol. 1986 Dec;16(12):1569–1575. doi: 10.1002/eji.1830161216. [DOI] [PubMed] [Google Scholar]
  19. Lortan J. E., Roobottom C. A., Oldfield S., MacLennan I. C. Newly produced virgin B cells migrate to secondary lymphoid organs but their capacity to enter follicles is restricted. Eur J Immunol. 1987 Sep;17(9):1311–1316. doi: 10.1002/eji.1830170914. [DOI] [PubMed] [Google Scholar]
  20. Mandel T. E., Phipps R. P., Abbot A., Tew J. G. The follicular dendritic cell: long term antigen retention during immunity. Immunol Rev. 1980;53:29–59. doi: 10.1111/j.1600-065x.1980.tb01039.x. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Näkelä O., Kaartinen M., Pelkonen J. L., Karjalainen K. Inheritance of antibody specificity V. Anti-2-phenyloxazolone in the mouse. J Exp Med. 1978 Dec 1;148(6):1644–1660. doi: 10.1084/jem.148.6.1644. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pelkonen J., Kaartinen M., Mäkelä O. Quantitative representation of two germ-line V genes in the early antibody response to 2-phenyloxazolone. Eur J Immunol. 1986 Jan;16(1):106–109. doi: 10.1002/eji.1830160120. [DOI] [PubMed] [Google Scholar]
  24. Rittenberg M. B., Pratt K. L. Antitrinitrophenyl (TNP) plaque assay. Primary response of Balb/c mice to soluble and particulate immunogen. Proc Soc Exp Biol Med. 1969 Nov;132(2):575–581. doi: 10.3181/00379727-132-34264. [DOI] [PubMed] [Google Scholar]
  25. Romball C. G., Weigle W. O. A cyclical appearance of antibody-producing cells after a single injection of serum protein antigen. J Exp Med. 1973 Dec 1;138(6):1426–1442. doi: 10.1084/jem.138.6.1426. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sprent J., Basten A. Circulating T and B lymphocytes of the mouse. II. Lifespan. Cell Immunol. 1973 Apr;7(1):40–59. doi: 10.1016/0008-8749(73)90181-0. [DOI] [PubMed] [Google Scholar]
  27. Tew J. G., Mandel T. The maintenance and regulation of serum antibody levels: evidence indicating a role for antigen retained in lymphoid follicles. J Immunol. 1978 Mar;120(3):1063–1069. [PubMed] [Google Scholar]
  28. Tew J. G., Phipps R. P., Mandel T. E. The maintenance and regulation of the humoral immune response: persisting antigen and the role of follicular antigen-binding dendritic cells as accessory cells. Immunol Rev. 1980;53:175–201. doi: 10.1111/j.1600-065x.1980.tb01044.x. [DOI] [PubMed] [Google Scholar]
  29. Weigle W. O. Cyclical production of antibody as a regulatory mechanism in the immune response. Adv Immunol. 1975;21:87–111. doi: 10.1016/s0065-2776(08)60219-9. [DOI] [PubMed] [Google Scholar]
  30. 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]

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