Engagement of the B-cell antigen receptor by antigen negatively regulates IgE production by antigen-specific B cells

Background: Functional differentiation of B lymphocytes can he regulated at different levels. Such B-cell responses, to a large extent, are under the control of T cells and the release of soluble factors from these cells. Crosslinking of B-cell antigen receptors also can direct B-cell differentiation, although the mechanisms are not well defined and the effects on specific antibody production have not been examined. Objective: This study was conducted to determine whether crosslinking of the B-cell antigen receptor hy antigen or antibody to the B-cell receptor could modulate specific antibody production, especially IgE production. Methods: Antigen-specific human B cells were isolated and incubated with antigen or antibody to the B-cell antigen receptor, Specific antibody production was examined, as were surface isotype expression and levels of Ig heavy chain mRNA in T cell-independent cultures. Results: The addition of antigen or anti-IgM antibody enhanced IgM and IgG antibody production in the presence of anti-CD40 and IL-4 but downregulated IgE synthesis. These changes in isotope production paralleled changes in the frequencies of surface Ig(+) B cells and Ig mRNA levels. Exogenous IL-6 abolished the antigen-mediated downregulation of IgE production. Conclusions: These studies indicate that signals delivered by means of the B-cell antigen receptor regulate antibody production in a distinct manner, resulting in enhanced IgM and IgG responses but leading to the inhibition of IgE production. Endogenous IL-6 production by B cells may counter the negative regulatory effects of antigen on IgE synthesis. We suggest that although antigen-mediated T/B-cell interactions play a major role in IgM- and IgG-specific antibody production, antigen-independent interactions may be more effective for T-cell dependent, IL-4-induced IgE production by antigen-specific B cells. Furthermore, these findings provide a basis for further understanding of allergic responses and modulation by immunotherapy, where repented exposure to large concentrations of allergen, administered by means of injection, enhance IgG responses and downregulate IgE synthesis.