IL-10 AND IL-13 AS B-CELL GROWTH AND DIFFERENTIATION FACTORS

B lymphocytes express at their surface the CD40 antigen which belongs to the NGF receptor superfamily. The crosslinking of the CD40 antigen using a mouse fibroblastic cell line expressing the human Fc receptor (FcgammaRII/CDw32) and anti-CD40 monoclonal antibody induces resting B lymphocytes to enter a state of sustained proliferation. Addition of IL-4 or IL-13 result in the proliferation of human B cells and in the secretion of IgE following isotype switching. Addition of IL-10 permit s limited cell proliferation but most importantly results in very high immunoglobulin production following differentiation of B cells into p lasma cells. In response to IL-10, unseparated B cells cultured in the CD40 system produce the four IgG subclasses in ratio comparable to th ose observed in the serum. IL-10 induces naive B cells to secrete low but reproducible amounts of IgG and IgA. The combination of IL-10 and TGFbeta induces naive B cells to secrete IgA1 and IgA2 as a consequenc e of isotype switching. The extracellular domain of CD40 binds with hi gh affinity and high specificity to a ligand transiently expressed on activated T cells. This interaction of the CD40 antigen on B cells wit h its counterstructure on T cells represents a key step in T cell depe ndent B cell activation.