CD40 LIGAND TRIGGERS INTERLEUKIN-6 MEDIATED B-CELL DIFFERENTIATION

Interleukin-6 (IL-6) is the major cytokine to date mediating antigen ( Ag)- or mitogen-driven B cell differentiation. Recently, CD40 ligand ( CD40L), with the co-stimulatory cytokines IL-4 and IL-10, has been sho wn to trigger immunoglobulin (Ig) secretion and class switching. In th e present report, we have examined the role of IL-6 in mediating B cel l differentiation and Ig secretion triggered with CD40L and/or these c ytokines. Culture of splenic B cells with CD40L triggered (1) signific ant (5.4-fold) increases in IL-6 secretion; (2) differentiation, evide nced by sequential loss of B cell (CD20, CD21) and acquisition of plas ma cell (CD38, PCA-1) surface antigens (Ags); and (3) Ig secretion. In terleukin-4 increased both IL-6 and IgG secretion stimulated by CD40L. Interleukin-10+ CD40L triggered 100-fold increments in IgG, IgA and I gM secretion, but IL-10 suppressed IL-6 secretion triggered with CD40L +/-IL-4. Exogenous IL-6 can further increase IgG secretion induced by CD40L + IL-10; moreover, the anti-IL-6 monoclonal antibody partially b locked IgG secretion triggered by CD40L+/-IL-4 or IL-10. Finally, IL-1 0 suppressed differentiation of B cells induced by CD40L. These studie s suggest that CD40L augments Ig secretion in at least two mechanisms: by triggering IL-6 secretion and related differentiation, and by prim ing B cells for responsiveness to IL-10. Copyright (C) 1996 Elsevier S cience Ltd.