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. 1974 Nov 30;140(6):1631–1645. doi: 10.1084/jem.140.6.1631

INDUCTION OF GUINEA PIG B-CELL LYMPHOKINE SYNTHESIS BY MITOGENIC AND NONMITOGENIC SIGNALS TO Fc, Ig, AND C3 RECEPTORS

S M Wahl 1, G M Iverson 1, J J Oppenheim 1
PMCID: PMC2139748  PMID: 4610080

Abstract

This study shows that bone marrow-derived lymphocytes of guinea pigs if appropriately activated produce a monocyte chemotactic factor (MNL CTX). Activation of B lymphocytes to produce a chemotactic lymphokine occurs subsequent to interactions with a variety of membrane-associated receptors. Polymeric B-cell mitogens with multiple binding sites, polymerized flagellin and lipopolysaccharide, initiated mediator synthesis. Furthermore, interaction of antigen-antibody complexes or aggregated gamma globulin with the Fc receptor and binding of antigen-antibody-complement complexes at the C3 receptor can effectively facilitate mediator production in the absence of a significant proliferative response. Additionally, intact anti-immunoglobulin but not its Fab fragments activated the B cells. An anti-Fab effectively converted the inactive Fab-bound B cells into producers of MNL CTX, suggesting that the basic mechanism of activation depended upon cross-linking of receptors. Thus, interaction of B-cell surface receptors such as Fc, Ig, and C3 sites with mitogenic as well as nonmitogenic molecules capable of bridging the receptors appears to trigger B-cell mediator production.

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Selected References

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  1. Alm G. V., Peterson R. D. Antibody and immunoglobulin production at the cellular level in bursectomized-irradiated chickens. J Exp Med. 1969 Jun 1;129(6):1247–1259. doi: 10.1084/jem.129.6.1247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Altman L. C., Kirchner H. The production of a monocyte chemotactic factor by agammaglobulinemic chicken spleen cells. J Immunol. 1972 Nov;109(5):1149–1151. [PubMed] [Google Scholar]
  3. 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]
  4. 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]
  5. Axén R., Porath J., Ernback S. Chemical coupling of peptides and proteins to polysaccharides by means of cyanogen halides. Nature. 1967 Jun 24;214(5095):1302–1304. doi: 10.1038/2141302a0. [DOI] [PubMed] [Google Scholar]
  6. Basten A., Sprent J., Miller J. F. Receptor for antibody-antigen complexes used to separate T cells from B cells. Nat New Biol. 1972 Feb 9;235(58):178–180. doi: 10.1038/newbio235178a0. [DOI] [PubMed] [Google Scholar]
  7. Basten A., Warner N. L., Mandel T. A receptor for antibody on B lymphocytes. II. Immunochemical and electron microscopy characteristics. J Exp Med. 1972 Mar 1;135(3):627–642. doi: 10.1084/jem.135.3.627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bianco C., Patrick R., Nussenzweig V. A population of lymphocytes bearing a membrane receptor for antigen-antibody-complement complexes. I. Separation and characterization. J Exp Med. 1970 Oct 1;132(4):702–720. doi: 10.1084/jem.132.4.702. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bretscher P. A., Cohn M. Minimal model for the mechanism of antibody induction and paralysis by antigen. Nature. 1968 Nov 2;220(5166):444–448. doi: 10.1038/220444a0. [DOI] [PubMed] [Google Scholar]
  10. Coutinho A., Gronowicz E., Bullock W. W., Möller G. Mechanism of thymus-independent immunocyte triggering. Mitogenic activation of B cells results in specific immune responses. J Exp Med. 1974 Jan 1;139(1):74–92. doi: 10.1084/jem.139.1.74. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dickler H. B., Kunkel H. G. Interaction of aggregated -globulin with B lymphocytes. J Exp Med. 1972 Jul 1;136(1):191–196. doi: 10.1084/jem.136.1.191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dukor P., Hartmann K. U. Hypothesis. Bound C3 as the second signal for B-cell activation. Cell Immunol. 1973 Jun;7(3):349–356. doi: 10.1016/0008-8749(73)90199-8. [DOI] [PubMed] [Google Scholar]
  13. Falcoff R., Oriol R., Iscaki S. Lymphocyte stimulation and interferon induction by 7 S anti-human lymphocyte globulins and their uni- and divalent fragments. Eur J Immunol. 1972 Oct;2(5):476–478. doi: 10.1002/eji.1830020520. [DOI] [PubMed] [Google Scholar]
  14. Fanger M. W., Hart D. A., Wells J. V., Nisonoff A. Requirement for cross-linkage in the stimulation of transformation of rabbit peripheral lymphocytes by antiglobulin reagents. J Immunol. 1970 Dec;105(6):1484–1492. [PubMed] [Google Scholar]
  15. Feldmann M., Easten A. The relationship between antigenic structure and the requirement for thymus-derived cells in the immune response. J Exp Med. 1971 Jul 1;134(1):103–119. doi: 10.1084/jem.134.1.103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Feldmann M., Nossal G. J. Tolerance, enhancement and the regulation of interactions between T cells, B cells and macrophages. Transplant Rev. 1972;13:3–34. doi: 10.1111/j.1600-065x.1972.tb00058.x. [DOI] [PubMed] [Google Scholar]
  17. Feldmann M., Pepys M. B. Role of C3 in in vitro lymphocyte cooperation. Nature. 1974 May 10;249(453):159–161. doi: 10.1038/249159a0. [DOI] [PubMed] [Google Scholar]
  18. Greaves M. F., Bauminger S., Janossy G. Lymphocyte activation. 3. Binding sites for phytomitogens on lymphocyte subpopulations. Clin Exp Immunol. 1972 Mar;10(3):537–554. [PMC free article] [PubMed] [Google Scholar]
  19. Greaves M., Janossy G. Elicitation of selective T and B lymphocyte responses by cell surface binding ligands. Transplant Rev. 1972;11:87–130. doi: 10.1111/j.1600-065x.1972.tb00047.x. [DOI] [PubMed] [Google Scholar]
  20. Hartzman R. J., Bach M. L., Bach F. H., Thurman G. B., Sell K. W. Precipitation of radioactively labeled samples: a semi-automatic multiple-sample processor. Cell Immunol. 1972 Jun;4(2):182–186. doi: 10.1016/0008-8749(72)90018-4. [DOI] [PubMed] [Google Scholar]
  21. Julius M. H., Simpson E., Herzenberg L. A. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973 Oct;3(10):645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
  22. Lay W. H., Nussenzweig V. Receptors for complement of leukocytes. J Exp Med. 1968 Nov 1;128(5):991–1009. doi: 10.1084/jem.128.5.991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Minna J. D., Iverson G. M., Herzenberg L. A. Identification of a gene locus for gamma-G-1 immunoglobulin H chains and its linkage to the H chain chromosome region in the mouse. Proc Natl Acad Sci U S A. 1967 Jul;58(1):188–194. doi: 10.1073/pnas.58.1.188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. NOWOTNY A. Relation of structure to function in bacterial O antigens. II. Fractionation of lipids present in Boivin-type endotoxin of Serratia marcescens. J Bacteriol. 1963 Feb;85:427–435. doi: 10.1128/jb.85.2.427-435.1963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Parker J. W., Metcalf D. Production of colony-stimulating factor in mitogen-stimulated lymphocyte cultures. J Immunol. 1974 Feb;112(2):502–510. [PubMed] [Google Scholar]
  26. Perlmann P., Perlmann H., Wigzell H. Lymphocyte mediated cytotoxicity in vitro. Induction and inhibition by humoral antibody and nature of effector cells. Transplant Rev. 1972;13:91–114. doi: 10.1111/j.1600-065x.1972.tb00061.x. [DOI] [PubMed] [Google Scholar]
  27. Pick E., Turk J. L. The biological activities of soluble lymphocyte products. Clin Exp Immunol. 1972 Jan;10(1):1–23. [PMC free article] [PubMed] [Google Scholar]
  28. Rocklin R. E. Production of migration inhibitory factor by non-dividing lymphocytes. J Immunol. 1973 Mar;110(3):674–678. [PubMed] [Google Scholar]
  29. Roos D., Loos J. A. Changes in the carbohydrate metabolism of mitogenically stimulated human peripheral lymphocytes. I. Stimulation by phytohaemagglutinin. Biochim Biophys Acta. 1970 Dec 29;222(3):565–582. doi: 10.1016/0304-4165(70)90182-0. [DOI] [PubMed] [Google Scholar]
  30. Rosenstreich D. L., Nowotny A., Chused T., Mergenhagen S. E. In vitro transformation of mouse bone-marrow-derived (B) lymphocytes induced by the lipid component of endotoxin. Infect Immun. 1973 Sep;8(3):406–411. doi: 10.1128/iai.8.3.406-411.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Schrader J. W. Mechanism of activation of the bone marrow-derived lymphocyte. 3. A distinction between a macrophage-produced triggering signal and the amplifying effect on triggered B lymphocytes of allogeneic interactions. J Exp Med. 1973 Dec 1;138(6):1466–1480. doi: 10.1084/jem.138.6.1466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Skamene E., Ivanyi J. Lymphocyte transformation by H-chain specific anti-immunoglobulin sera. Nature. 1969 Feb 15;221(5181):681–682. doi: 10.1038/221681a0. [DOI] [PubMed] [Google Scholar]
  33. Stadecker M. J., Bishop G., Wortis H. H. Rosette formation by guinea pig thymocytes and thymus derived lymphocytes with rabbit red blood cells. J Immunol. 1973 Dec;111(6):1834–1837. [PubMed] [Google Scholar]
  34. Wahl S. M., Altman L. C., Oppenheim J. J., Mergenhagen S. E. In vitro studies of a chemotactic lymphokine in the guinea pig. Int Arch Allergy Appl Immunol. 1974;46(5):768–784. doi: 10.1159/000231176. [DOI] [PubMed] [Google Scholar]
  35. Ward P. A., Remold H. G., David J. R. The production by antigen-stimulated lymphocytes of a leukotactic factor distinct from migration inhibitory factor. Cell Immunol. 1970 Jul;1(2):162–174. doi: 10.1016/0008-8749(70)90003-1. [DOI] [PubMed] [Google Scholar]
  36. Wilson A. B., Coombs R. R. Rosette-formation between guinea pig lymphoid cells and rabbit erythrocytes--a possible T-cell marker. Int Arch Allergy Appl Immunol. 1973;44(4):544–552. doi: 10.1159/000230959. [DOI] [PubMed] [Google Scholar]
  37. Woodruff M. F., Reid B., James K. Effect of antilymphocytic antibody and antibody fragments on human lymphocytes in vitro. Nature. 1967 Aug 5;215(5101):591–594. doi: 10.1038/215591a0. [DOI] [PubMed] [Google Scholar]
  38. Yoshida T., Sonozaki H., Cohen S. The production of migration inhibition factor by B and T cells of the guinea pig. J Exp Med. 1973 Oct 1;138(4):784–797. doi: 10.1084/jem.138.4.784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. van Boxel J. A., Hardin J. A., Green I., Paul W. E. Multiple heavy-chain determinants on individual B lymphocytes in the peripheral blood of patients with Sjögren's syndrome. N Engl J Med. 1973 Oct 18;289(16):823–827. doi: 10.1056/NEJM197310182891602. [DOI] [PubMed] [Google Scholar]

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