Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1975 Nov 1;142(5):1165–1179. doi: 10.1084/jem.142.5.1165

The allogeneic bisection of carrier-specific enhancement of monoclonal B-cell responses

PMCID: PMC2189964  PMID: 811749

Abstract

The ability of T cells to enhance the response of syngeneic and allogeneic B cells to thymus-dependent hapten-carrier conjugates was analyzed. This analysis was carried out on individual primary B cells in splenic fragment cultures derived from irradiated reconstituted mice. This system has several advantages: (a) the response of the B cells is entirely dependent on carrier priming of the irradiated recipient; (b) this B-cell response can be quantitated in terms of the number of responding cells; and (c) very small B-cell responses can be readily detected and analyzed. The results indicate that the majority of hapten-specific B cells were stimulated in allogeneic and syngeneic recipients only if these recipients were previously carrier primed. The number of B cells responding in carrier-primed allogeneic recipients was 60-70% of that in syngeneic carrier-primed recipients. The antibody- forming cell clones resulting from B cells stimulated in the allogeneic environment produced small amounts of antibody and antibody solely of the IgM immunoglobulin class, while the larger responses in syngeneic recipients were predominantly IgG1 or IgM plus IgG1. The capacity of collaborative interactions between carrier-primed T cells and primary B cells to yield IgG1 antibody-producing clones was shown to be dependent on syngeny between these cells in the H-2 gene complex. It is concluded that: (a) B cells can be triggered by T-dependent antigens to clone formation through collaboration with T cells which differ at the H-2 complex as long as these T cells recognize the antigen; (b) the immunoglobulin class produced by the progeny of stimulated B cells generally depends on the nature of the stimulatory event rather than the nature of the B cell itself; and (c) stimulation to IgG1 production is dependent on syngeny between the collaborating T and B cells probably within the Ir-1A region. The role of the Ia antigens in the formation of IgG1-producing clones is not yet clear; Ia identity could permit IgG1 production or, conversely, nonidentity of Ia could induce all allogeneic interactions which prohibit IgG1 production.

Full Text

The Full Text of this article is available as a PDF (976.8 KB).

Selected References

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

  1. Ada G. L., Byrt P. Specific inactivation of antigen-reactive cells with 125I-labelled antigen. Nature. 1969 Jun 28;222(5200):1291–1292. doi: 10.1038/2221291a0. [DOI] [PubMed] [Google Scholar]
  2. Armerding D., Katz D. H. Activation of T and B lymphocytes in vitro. II. Biological and biochemical properties of an allogeneic effect factor (AEF) active in triggering specific B lymphocytes. J Exp Med. 1974 Jul 1;140(1):19–37. doi: 10.1084/jem.140.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Armerding D., Sachs D. H., Katz D. H. Activation of T and B lymphocytes in vitro. III. Presence of Ia determinants on allogeneic effect factor. J Exp Med. 1974 Dec 1;140(6):1717–1722. doi: 10.1084/jem.140.6.1717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baker P. J., Stashak P. W., Amsbaugh D. F., Prescott B. Regulation of the antibody response to type 3 pneumococcal polysaccharide. II. Mode of action of thymic-derived suppressor cells. J Immunol. 1974 Jan;112(1):404–409. [PubMed] [Google Scholar]
  5. Bechtol K. B., Freed J. H., Herzenberg L. A., McDevitt H. O. Genetic control of the antibody response to poly-L(Tyr,Glu)-poly-D,L-Ala--poly-L-Lys in C3H--CWB tetraparental mice. J Exp Med. 1974 Dec 1;140(6):1660–1675. doi: 10.1084/jem.140.6.1660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Claman H. N., Chaperon E. A., Triplett R. F. Thymus-marrow cell combinations. Synergism in antibody production. Proc Soc Exp Biol Med. 1966 Aug-Sep;122(4):1167–1171. doi: 10.3181/00379727-122-31353. [DOI] [PubMed] [Google Scholar]
  7. Cosenza H., Köhler H. Specific inhibition of plaque formation to phosphorylcholine by antibody against antibody. Science. 1972 Jun 2;176(4038):1027–1029. doi: 10.1126/science.176.4038.1027. [DOI] [PubMed] [Google Scholar]
  8. Coutinho A., Möller G. Editorial: Immune activation of B cells: evidence for 'one nonspecific triggering signal' not delivered by the Ig receptors. Scand J Immunol. 1974;3(2):133–146. [PubMed] [Google Scholar]
  9. Doughty R. A., Klinman N. R. Carrier independent T cell helper effects in antigenic stimulation. J Immunol. 1973 Oct;111(4):1140–1146. [PubMed] [Google Scholar]
  10. Feldmann M. Induction of immunity and tolerance in vitro by hapten protein conjugates. II. Carrier independence of the response to dinitrophenylated polymerized flagellin. Eur J Immunol. 1972 Apr;2(2):130–137. doi: 10.1002/eji.1830020208. [DOI] [PubMed] [Google Scholar]
  11. Gearhart P. J., Sigal N. H., Klinman N. R. Heterogeneity of the BALB/c antiphosphorylcholine antibody response at the precursor cell level. J Exp Med. 1975 Jan 1;141(1):56–71. doi: 10.1084/jem.141.1.56. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gearhart P. J., Sigal N. H., Klinman N. R. Production of antibodies of identical idiotype but diverse immunoglobulin classes by cells derived from a single stimulated B cell. Proc Natl Acad Sci U S A. 1975 May;72(5):1707–1711. doi: 10.1073/pnas.72.5.1707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hamaoka T., Osborne D. P., Jr, Katz D. H. Cell interactions between histoincompatible T and B lymphocytes. I. Allogeneic effect by irradiated host T cells on adoptively transferred histoincompatible B lymphocytes. J Exp Med. 1973 Jun 1;137(6):1393–1404. doi: 10.1084/jem.137.6.1393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Heber-Katz E., Wilson D. B. Collaboration of allogeneic T and B lymphocytes in the primary antibody response to sheep erythrocytes in vitro. J Exp Med. 1975 Oct 1;142(4):928–935. doi: 10.1084/jem.142.4.928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Howard J. G., Christie G. H., Courtenay B. M., Leuchars E., Davies A. J. Studies on immunological paralysis. VI. Thymic-independence of tolerance and immunity to type 3 pneumococcal polysaccharide. Cell Immunol. 1971 Dec;2(6):614–626. doi: 10.1016/0008-8749(71)90009-8. [DOI] [PubMed] [Google Scholar]
  16. Katz D. H., Graves M., Dorf M. E., Dimuzio H., Benacerraf B. Cell interactions between histoincompatible T and B lymphocytes. VII. Cooperative responses between lymphocytes are controlled by genes in the I region of the H-2 complex. J Exp Med. 1975 Jan 1;141(1):263–268. doi: 10.1084/jem.141.1.263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Katz D. H., Paul W. E., Goidl E. A., Benacerraf B. Carrier function in anti-hapten antibody responses. 3. Stimulation of antibody synthesis and facilitation of hapten-specific secondary antibody responses by graft-versus-host reactions. J Exp Med. 1971 Feb 1;133(2):169–186. doi: 10.1084/jem.133.2.169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Klaus G. G., Humphrey J. H. Mechanisms of b cell triggering: studies with t cell-independent antigens. Transplant Rev. 1975;23:105–118. doi: 10.1111/j.1600-065x.1975.tb00152.x. [DOI] [PubMed] [Google Scholar]
  19. Klinman N. R., Doughty R. A. Hapten-specific stimulation of secondary B cells independent of T cells. J Exp Med. 1973 Aug 1;138(2):473–478. doi: 10.1084/jem.138.2.473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Klinman N. R., Press J. L. The B cell specificity repertoire: its relationship to definable subpopulations. Transplant Rev. 1975;24:41–83. doi: 10.1111/j.1600-065x.1975.tb00165.x. [DOI] [PubMed] [Google Scholar]
  21. Klinman N. R. Purification and analysis of "monofocal" antibody. J Immunol. 1971 May;106(5):1345–1352. [PubMed] [Google Scholar]
  22. Klinman N. R. The mechanism of antigenic stimulation of primary and secondary clonal precursor cells. J Exp Med. 1972 Aug 1;136(2):241–260. doi: 10.1084/jem.136.2.241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Klinman N. R. The secondary immune response to a hapten in vitro. Antigen concentration and the carrier effect. J Exp Med. 1971 May 1;133(5):963–972. doi: 10.1084/jem.133.5.963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Miller J. F., Mitchell G. F. Cell to cell interaction in the immune response. I. Hemolysin-forming cells in neonatally thymectomized mice reconstituted with thymus or thoracic duct lymphocytes. J Exp Med. 1968 Oct 1;128(4):801–820. doi: 10.1084/jem.128.4.801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mitchison N. A. The carrier effect in the secondary response to hapten-protein conjugates. II. Cellular cooperation. Eur J Immunol. 1971 Jan;1(1):18–27. doi: 10.1002/eji.1830010104. [DOI] [PubMed] [Google Scholar]
  26. Press J. L., Klinman N. R. Enumeration and analysis of antibody-forming cell precursors in the neonatal mouse. J Immunol. 1973 Sep;111(3):829–835. [PubMed] [Google Scholar]
  27. Press J. L., Klinman N. R. Monoclonal production of both IgM and IgG1 antihapten antibody. J Exp Med. 1973 Jul 1;138(1):300–305. doi: 10.1084/jem.138.1.300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. REIF A. E., ALLEN J. M. THE AKR THYMIC ANTIGEN AND ITS DISTRIBUTION IN LEUKEMIAS AND NERVOUS TISSUES. J Exp Med. 1964 Sep 1;120:413–433. doi: 10.1084/jem.120.3.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Raff M. C., Feldmann M., De Petris S. Monospecificity of bone marrow-derived lymphocytes. J Exp Med. 1973 Apr 1;137(4):1024–1030. doi: 10.1084/jem.137.4.1024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Rubin A. S., Coons A. H. Specific heterologous enhancement of immune responses. 3. Partial characterization of supernatant material with enhancing activity. J Immunol. 1972 Jun;108(6):1597–1604. [PubMed] [Google Scholar]
  31. Schrader J. W. Induction of immunological tolerance to a thymus-dependent antigen in the absence of thymus-derived cells. J Exp Med. 1974 May 1;139(5):1303–1316. doi: 10.1084/jem.139.5.1303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Schrader J. W. The role of T cells in IgG production; thymus-dependent antigens induce B cell memory in the absence of T cells. J Immunol. 1975 Jun;114(6):1665–1669. [PubMed] [Google Scholar]
  33. Sharon R., McMaster P. R., Kask A. M., Owens J. D., Paul W. E. DNP-Lys-ficoll: a T-independent antigen which elicits both IgM and IgG anti-DNP antibody-secreting cells. J Immunol. 1975 May;114(5):1585–1589. [PubMed] [Google Scholar]
  34. Shreffler D. C., David C. S. The H-2 major histocompatibility complex and the I immune response region: genetic variation, function, and organization. Adv Immunol. 1975;20:125–195. doi: 10.1016/s0065-2776(08)60208-4. [DOI] [PubMed] [Google Scholar]
  35. Sigal N. H., Gearhart P. J., Klinman N. R. The frequency of phosphorylcholine-specific B cells in conventional and germfree BALB/C mice. J Immunol. 1975 Apr;114(4):1354–1358. [PubMed] [Google Scholar]
  36. Trenkner E. The use of allogeneic T lymphocytes and bacterial lipopolysaccharide to induce immune responses to monovalent haptens in vitro. J Immunol. 1974 Sep;113(3):918–924. [PubMed] [Google Scholar]
  37. Wigzell H., Mäkelä O. Separation of normal and immune lymphoid cells by antigen-coated coated columns. Antigen-binding characteristics of membrane antibodies as analyzed by hapten-protein antigens. J Exp Med. 1970 Jul 1;132(1):110–126. doi: 10.1084/jem.132.1.110. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES