Reciprocal regulation of mucosal surface IgA+ B cells by Ig receptor cross-linking and CD40 ligand.

In the present study, we analyze the role of Ig receptor cross-linking in T cell-dependent stimulation of both preswitch (surface IgM+ (sIgM+/sIgD+) B cells and postswitch (sIgA+) B cells. We demonstrate that purified sIgA+ B cells pretreated with anti-IgA-dextran at low concentrations (10 and 100 ng/ml) exhibited an increased response to activated T cells, whereas pretreatment with higher doses (1 and 10 micrograms/ml) led to a profound suppression of IgA secretion (> or = 90%). The suppressive effect of anti-IgA-dextran was accentuated in the presence of IL-2 and attenuated in the presence of IL-4. Anti-IgA-dextran pretreatment had no effect on sIgA+ B cell survival. sIgM+/sIgD+ B cells pretreated with anti-IgD-dextran or anti-IgM-dextran did not show significant inhibition. The increased susceptibility of sIgA+ B cells, but not of sIgM+/sIgD+ B cells, to Ig cross-linking-mediated suppression was confirmed in cross-linking studies with the same Ab (anti-kappa-dextran). Importantly, anti-IgA-dextran-mediated suppression could be reversed by stimulation of sIgA+ B cells with fibroblasts expressing CD40L; such a reversal required persistent exposure to cells expressing high levels of CD40L. These studies imply that Ig receptor cross-linking renders postswitch sIgA+ B cells unresponsive to subsequent stimulation via activated T cells, but this unresponsiveness is overcome by a persistent high level CD40L signal.