T-dependent B Lymphocyte Activation Mechanisms Discussed

In the Th cell-dependent antibody response, the Th activate B cells via both cell contact and soluble factors. Both signals are generally believed to be essential for B cell proliferation as well as for Ig secretion. In our study, a mutant EL-4 thymoma cells of mouse origin was used as Th cells to investigate the mechanism of T-dependent B cell response. We found some new mechanisms of this response after studying the dependence of B cell activation on Th cell contact or on cytokines released by Th cell, the production of cytokine mRNA by human normal B cells before and after activation and the influence of exogenous cytokines on B cell differentiation. Besides the activation of human B cells by EL-4 cells in the conjunction of T cell supernatant (T-sup) , it was found that EL-4 cells pretreated with PMA activate human B cells directly in the absence of human T-sup. The PMA induced EL-4 activity, which occurs via cell-contact and is cyclosporin A (CsA) sensitive, is probably the nevol membrane protein(s) but not cytokines produced by EL-4 cells. Any contribution of soluble factors from contaminating human T cells was ruled out by adding single human B cells by microflurimetry to cultures with EL-4 cells and PMA, which gave similar immunoglobulin isotype secretion and distribution as EL-4 cells plus T-SUP. CsA, thus interfered with some cell contact-mediated signal. The sources of cytokines have been detected by reverse transcription / polymerase chain reaction (RT/PCR). It was found that human B cells may express may cytokines mRNAs, including the mRNA of IL-1α, IL-1β, IL-6, IL-10, TNFγ and TGFβ .The changes of mRNA expression have been observed during the B cell activation and differentiation. The kinetics of IL-6 and TNFα correspond to that of B cell proliferation. mRNA of TGFβ and IL-10 exsit during the whole culture period. Exogenous IL-4 induces the reappearance of IL-la mRNA and increases the signals of IL-6 and TNFa. Among the exogenous cytokines, IL-4 is the only one that increases IgE production in EL-4/B cell culture system. The increase of IgE production by IL-4 results from both induction of IgE class switch and promotion of IgE secreting from already IgE-committed B cells in vivo. IL-4 induces IgE class switch frequently from surface IgM + and sIgA +...