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. 1980 Mar 1;151(3):587–601. doi: 10.1084/jem.151.3.587

Specific T helper cells that activate B cells polyclonally. In vitro enrichment and cooperative function

PMCID: PMC2185802  PMID: 6766981

Abstract

C3H/HeJ T cells which specifically recognize B cell-surface antigens of the related, major histocompatibility complex-compatible C3H/Tif strain, can be substantially enriched in vitro by long-term exposure (2- -6 wk) of primed lymph node cells to the relevant cellular antigens. These enriched T cells contain functional helper cells as demonstrated by their capacity to induce large numbers of Ig-secreting plaque- forming cells (PFC) in cultures of antigenic B cells. The cooperative interaction results in activation of a large fraction of all splenic B cells, with consequent exponential growth and maturation to high rate secretion of IgM, IgG1, and IgG2, but not IgG3. The IgM PFC response includes antibody specificities to a number of different antigens and can be considered, therefore, as polyclonal. The T helper cell- dependent B-cell response is insensitive to inhibition by anti-delta antibodies, and in contrast with lipopolysaccharide-induced PFC responses, is only partially sensitive to the inhibitory effects of anti-mu antibodies. Finally, B-cell activation to growth and maturation by helper T cells strictly required direct T-cell recognition of antigens on the surface of responding B cells, leading us to the conclusions that if any soluble factors are generated in the collaborative process, they are either antigen specific or incompetent to initiate B-cell growth.

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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 B., Blomgren H. T-cell response to polyvinyl pyrrolidone is linked to maturity of B cells. Nature. 1975 Feb 6;253(5491):476–477. doi: 10.1038/253476a0. [DOI] [PubMed] [Google Scholar]
  2. Andersson J., Bullock W. W., Melchers F. Inhibition of mitogenic stimulation of mouse lymphocytes by anti-mouse immunoglobulin antibodies. I. Mode of action. Eur J Immunol. 1974 Nov;4(11):715–722. doi: 10.1002/eji.1830041103. [DOI] [PubMed] [Google Scholar]
  3. Andersson J., Coutinho A., Lernhardt W., Melchers F. Clonal growth and maturation to immunoglobulin secretion in vitro of every growth-inducible B lymphocyte. Cell. 1977 Jan;10(1):27–34. doi: 10.1016/0092-8674(77)90136-2. [DOI] [PubMed] [Google Scholar]
  4. Andersson J., Coutinho A., Melchers F. Frequencies of mitogen-reactive B cells in the mouse. I. Distribution in different lymphoid organs from different inbred strains of mice at different ages. J Exp Med. 1977 Jun 1;145(6):1511–1519. doi: 10.1084/jem.145.6.1511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Andersson J., Coutinho A., Melchers F. Frequencies of mitogen-reactive B cells in the mouse. II. Frequencies of B cells producing antibodies which lyse sheep or horse erythrocytes, and trinitrophenylated or nitroiodophenylated sheep erythrocytes. J Exp Med. 1977 Jun 1;145(6):1520–1530. doi: 10.1084/jem.145.6.1520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Andersson J., Coutinho A., Melchers F., Watanabe T. Growth and maturation of single clones of normal murine T and B lymphocytes in vitro. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 1):227–236. doi: 10.1101/sqb.1977.041.01.028. [DOI] [PubMed] [Google Scholar]
  7. Andersson J., Sjöberg O., Möller G. Mitogens as probes for immunocyte activation and cellular cooperation. Transplant Rev. 1972;11:131–177. doi: 10.1111/j.1600-065x.1972.tb00048.x. [DOI] [PubMed] [Google Scholar]
  8. Augustin A. A., Julius M. H., Cosenza H. Antigen-specific stimulation and trans-stimulation of T cells in long-term culture. Eur J Immunol. 1979 Sep;9(9):665–670. doi: 10.1002/eji.1830090903. [DOI] [PubMed] [Google Scholar]
  9. Cambier J. C., Ligler F. S., Uhr J. W., Kettman J. R., Vitetta E. S. Blocking of primary in vitro antibody responses to thymus-independent and thymus-dependent antigens with antiserum specific for IgM or IgD. Proc Natl Acad Sci U S A. 1978 Jan;75(1):432–435. doi: 10.1073/pnas.75.1.432. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cammisuli S., Henry C., Wofsy L. Role of membrane receptors in the induction of an in vitro secondary anti-hapten response. I. differentiation of B memory cells to plasma cells is independent of antigen-immunoglobulin receptor interaction. Eur J Immunol. 1978 Sep;8(9):656–662. doi: 10.1002/eji.1830080910. [DOI] [PubMed] [Google Scholar]
  11. Chiorazzi N., Fu S. M., Kunkel H. G. Induction of polyclonal antibody synthesis by human allogeneic and autologous helper factors. J Exp Med. 1979 Jun 1;149(6):1543–1548. doi: 10.1084/jem.149.6.1543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Coutinho A., Forni L., Watanabe T. Genetic and functional characterization of an antiserum to the lipid A-specific triggering receptor on murine B lymphocytes. Eur J Immunol. 1978 Jan;8(1):63–67. doi: 10.1002/eji.1830080113. [DOI] [PubMed] [Google Scholar]
  13. Coutinho A., Möller G. Thymus-independent B-cell induction and paralysis. Adv Immunol. 1975;21:113–236. doi: 10.1016/s0065-2776(08)60220-5. [DOI] [PubMed] [Google Scholar]
  14. Eichmann K., Coutinho A., Melchers F. Absolute frequencies of lipopolysaccharide-reactive B cells producing A5A idiotype in unprimed, streptococcal A carbohydrate-primed, anti-A5A idiotype-sensitized and anti-A5A idiotype-suppressed A/J mice. J Exp Med. 1977 Nov 1;146(5):1436–1449. doi: 10.1084/jem.146.5.1436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Eichmann K., Falk I., Rajewsky K. Recognition of idiotypes in lymphocyte interactions. II. Antigen-independent cooperation between T and B lymphocytes that possess similar and complementary idiotypes. Eur J Immunol. 1978 Dec;8(12):853–857. doi: 10.1002/eji.1830081206. [DOI] [PubMed] [Google Scholar]
  16. Forni L., Coutinho A. An antiserum which recognizes lipopolysaccharide-reactive B cells in the mouse. Eur J Immunol. 1978 Jan;8(1):56–62. doi: 10.1002/eji.1830080112. [DOI] [PubMed] [Google Scholar]
  17. Geha R. S., Mudawwar F., Schneeberger E. The specificity of T-cell helper factor in man. J Exp Med. 1977 Jun 1;145(6):1436–1448. doi: 10.1084/jem.145.6.1436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Goding J. W. Conjugation of antibodies with fluorochromes: modifications to the standard methods. J Immunol Methods. 1976;13(3-4):215–226. doi: 10.1016/0022-1759(76)90068-5. [DOI] [PubMed] [Google Scholar]
  19. Gorczynski R. M., Feldmann M. B Cell heterogeneity - difference in the size of B lymphocytes responding to T dependent and T independent antigens. Cell Immunol. 1975 Jul;18(1):88–97. doi: 10.1016/0008-8749(75)90039-8. [DOI] [PubMed] [Google Scholar]
  20. Gronowicz E., Coutinho A. Functional analysis of B cell heterogeneity. Transplant Rev. 1975;24:3–40. doi: 10.1111/j.1600-065x.1975.tb00164.x. [DOI] [PubMed] [Google Scholar]
  21. Gronowicz E., Coutinho A., Melchers F. A plaque assay for all cells secreting Ig of a given type or class. Eur J Immunol. 1976 Aug;6(8):588–590. doi: 10.1002/eji.1830060812. [DOI] [PubMed] [Google Scholar]
  22. Kearney J. F., Klein J., Bockman D. E., Cooper M. D., Lawton A. R. B cell differentiation induced by lipopolysaccharide. V. Suppression of plasma cell maturation by anti-mu: mode of action and characteristics of suppressed cells. J Immunol. 1978 Jan;120(1):158–166. [PubMed] [Google Scholar]
  23. Kearney J. F., Lawton A. R. B lymphocyte differentiation induced by lipopolysaccharide. I. Generation of cells synthesizing four major immunoglobulin classes. J Immunol. 1975 Sep;115(3):671–676. [PubMed] [Google Scholar]
  24. Lewis G. K., Ranken R., Nitecki D. E., Goodman J. W. Murine B-cell subpopulations responsive to T-dependent and T-independent antigens. J Exp Med. 1976 Aug 1;144(2):382–397. doi: 10.1084/jem.144.2.382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Marrack P., Kappler J. W. The role of H-2-linked genes in helper T-cell function. III. Expression of immune response genes for trinitrophenyl conjugates of poly-L(Tyr, Glu)-poly-D,L-Ala--poly-L-Lys in B cells and macrophages. J Exp Med. 1978 Jun 1;147(6):1596–1610. doi: 10.1084/jem.147.6.1596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Melchers F., Andersson J., Phillips R. A. Ontogeny of murine B lymphocytes: development of Ig synthesis and of reactivities to mitogens and to anti-Ig-antibodies. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 1):147–158. doi: 10.1101/sqb.1977.041.01.019. [DOI] [PubMed] [Google Scholar]
  27. Melchers F., Andersson J. Synthesis, surface deposition and secretion of immunoglobulin M in bone marrow-derived lymphocytes before and after mitogenic stimulation. Transplant Rev. 1973;14:76–130. doi: 10.1111/j.1600-065x.1973.tb00103.x. [DOI] [PubMed] [Google Scholar]
  28. Quintáns J., Cosenza H. Antibody response to phosphorylcholine in vitro. II. Analysis of T-dependent and T-independent responses. Eur J Immunol. 1976 Jun;6(6):399–405. doi: 10.1002/eji.1830060605. [DOI] [PubMed] [Google Scholar]
  29. Sprent J. Restricted helper function of F1 hybrid T cells positively selected to heterologous erythrocytes in irradiated parental strain mice. II. Evidence for restrictions affecting helper cell induction and T-B collaboration, both mapping to the K-end of the H-2 complex. J Exp Med. 1978 Apr 1;147(4):1159–1174. doi: 10.1084/jem.147.4.1159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Waterfield J. D., Dennert G., Swain S. L., Dutton R. W. Continuously proliferating allospecific T cells. I. Specificity of cooperation with allogeneic B cells in the humoral antibody response to sheep erythrocytes. J Exp Med. 1979 Apr 1;149(4):808–814. doi: 10.1084/jem.149.4.808. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Watson J., Kelly K., Largen M., Taylor B. A. The genetic mapping of a defective LPS response gene in C3H/HeJ mice. J Immunol. 1978 Feb;120(2):422–424. [PubMed] [Google Scholar]
  32. Woodland R., Cantor H. Idiotype-specific T helper cells are required to induce idiotype-positive B memory cells to secrete antibody. Eur J Immunol. 1978 Aug;8(8):600–606. doi: 10.1002/eji.1830080812. [DOI] [PubMed] [Google Scholar]
  33. Zitron I. M., Mosier D. E., Paul W. E. The role of surface IgD in the response to thymic-independent antigens. J Exp Med. 1977 Dec 1;146(6):1707–1718. doi: 10.1084/jem.146.6.1707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. von Boehmer H., Sprent J. Expression of M locus differences by B cells but not T cells. Nature. 1974 May 24;249(455):363–365. doi: 10.1038/249363a0. [DOI] [PubMed] [Google Scholar]

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