Soluble factor-independent stimulation of human B cell response by mouse thymoma cells. Cyclosporine A-resistant and -sensitive cell contact signals.
In a Th cell-dependent antibody response, the Th act on B cells partly via a helper activity that is cell contact-dependent and cyclosporine A (CsA)-resistant. This activity seems to be required to induce responsiveness of the B cells toward T cell-derived soluble factors (cytokines) generally believed to be essential for B cell proliferation as well as for Ig secretion. In our study, we have investigated a system in which human B cells are stimulated by mutant EL-4 thymoma cells of mouse origin. It was found that human B cells proliferate and secrete Ig (either 1) in the presence of EL-4 cells plus human T cell supernatant (T-SUP), or 2) in the presence of EL-4 cells alone which have been induced with PMA or IL-1. The first situation conformed to the known synergy between CsA-resistant Th signal and cytokines. However, the B response due to PMA-induced EL-4 cells was special. The PMA-inducible helper activity was CsA-sensitive at the same CsA concentration that inhibited IL-2 secretion of EL-4 cells, but the murine factors in EL-4 supernatant had no effect on human B cells; the helper effect did not occur across a semipermeable membrane. Any contribution of soluble factors from contaminating human T cells was ruled out by adding single human B cells by flow microfluorimetry to cultures with EL-4 cells and PMA. Such B cells generated clonal IgM, IgG, and/or IgA responses. CsA, thus, interfered with some cell contact-mediated signal. However, CsA did not reduce the amount of LFA-1 molecules on EL-4 cells. In conclusion, EL-4 cells can induce proliferation and differentiation of human B cells in a soluble factor-independent manner, via CsA-resistant and CsA-sensitive helper activities. This may represent an alternative pathway of B cell activation.
Zhang
X H
XH
Department of Medicine, Hôpital Cantonal Universitaire, Genève, Switzerland.
Hauser
C
C
Zubler
R H
RH
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology*; D002448:Cell Adhesion; D002450:Cell Communication; D003524:Cyclosporins / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D016169:Lymphocyte Function-Associated Antigen-1; D008222:Lymphokines / Q000502:physiology; D051379:Mice; D016028:Receptors, Leukocyte-Adhesion / Q000032:analysis; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000943:Antigens, Differentiation; D003524:Cyclosporins; D016169:Lymphocyte Function-Associated Antigen-1; D008222:Lymphokines; D016028:Receptors, Leukocyte-Adhesion; D013755:Tetradecanoylphorbol Acetate