B lymphocytes regulate dendritic cell (DC) function in vivo: Increased interleukin 12 production by DCs from B cell-deficient mice results in T helper cell type 1 deviation

Increasing evidence indicates that dendritic cells (DCs) are the antigen-pr esenting cells of the primary immune response. However, several reports sug gest that B lymphocytes could be required for optimal T cell sensitization. We compared the immune responses of wild-type and B cell-deficient (mu MT) mice, induced by antigen emulsified in adjuvant or pulsed on splenic dendr itic cells. Our data show that lymph node cells from both control and mu MT animals were primed, but each released distinct cytokine profiles. Lymph n ode T cells from control animals secreted interferon (IFN)-gamma, interleuk in (IL)-2, and IL-4, whereas those from mu MT mice produced IFN-gamma and I L-2 but no IL-4. To test whether B cells may influence the T helper cell ty pe 1 (Th1)/Th2 balance by affecting the function of DCs, we immunized mice by transferring antigen-pulsed DCs from wild-type or mutant mice. Injection of control DCs induced the secretion of IL-4, IFN-gamma, and IL-2, whereas administration of DCs from mu MT animals failed to sensitize cells to prod uce IL-4. Analysis of IL-12 production revealed that DCs from mu MT mice pr oduce higher levels of IL-12p70 than do DCs from wild-type animals. These d ata suggest that B lymphocytes regulate the capacity of DCs to promote IL-4 secretion, possibly by downregulating their secretion of IL-12, thereby fa voring the induction of a nonpolarized immune response.