ANTIGEN-SPECIFIC B-CELLS PREFERENTIALLY INDUCE CD4(-CELLS TO PRODUCE IL-4() T)

The role of Ag presentation by B cells in regulating the development o f T cells with restricted cytokine profiles remains controversial. In this report, we compared Ag presentation by naive polyclonal B cells, naive Ag-specific B cells (from Ig receptor transgenic mice), or splen ic adherent cells (SAC) and examined the capacity of these cells to in fluence cytokine production by CD4(+) T cells. Freshly isolated naive B cells stimulated vigorous T cell proliferation and very strong T cel l cytokine responses, but only when cultured with Ag recognized by the B cell Ig receptor (cognate Ag) and not when cultured with a noncogna te Ag. Under these conditions, B cells activated by Ig receptor-mediat ed endocytosis of Ag induced both naive and Ag-primed CD4(+) T cells t o produce high levels of IL-4 (300-4000 pg/ml). In contrast, SAC induc ed the production of very low levels of IL-4 (<100 pg/ml) but much hig her maximal levels of IFN-gamma than did Ag-specific B cells. The indu ction of IL-4 synthesis by Ag-specific B cells was significantly reduc ed by blocking CD40-CD40 ligand (CD40L) interactions or by the additio n of small quantities of rIL-12. These results suggest that B cells ac tivated by their cognate Ag preferentially induce IL-4 synthesis as a result of the interaction of CD40L on T cells with CD40, whereas SAC p referentially induce IFN-gamma synthesis by T cells as a result of the ir greater production of IL-12 and their limited capacity to trigger C D40L on T cells.