RECIPROCAL REGULATION OF MUCOSAL SURFACE IGA(-CELLS BY IG RECEPTOR CROSS-LINKING AND CD40 LIGAND() B)

In the present study, we analyze the role of Ig receptor cross-linking in T cell-dependent stimulation of both preswitch surface IgM(+) (sIg m(+)/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 mu g/ml) led to a profound suppression of IgA secretion (greater than or equal to 90%). The suppressive effect of anti-IgA-dextran was accentu ated in the presence of IL-2 and attenuated in the presence of IL-4. A nti-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 susceptibil ity of sIgA(+) B cells, but not of sIgM(+)/sIgD(+) B cells, to Ig cros s-linking-mediated suppression was confirmed in cross-linking studies with the same Ab (anti-kappa-dextran) Importantly, anti-IgA-dextran-me diated suppression could be reversed by stimulation of sIgA(+) B cells with fibroblasts expressing CD40L; such a reversal required persisten t exposure to cells expressing high levels of CD40L. These studies imp ly that Ig receptor cross-linking renders postswitch sIga(+) B cells u nresponsive to subsequent stimulation via activated T cells, but this unresponsiveness is overcome by a persistent high level CD40L signal.