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 (Fc gamma RII/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 permits limited cell proliferation but most importantly results in very high immunoglobulin production following differentiation of B cells into plasma cells. In response to IL-10, unseparated B cells cultured in the CD40 system produced the four IgG subclasses in ratio comparable to those 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 TGF beta induces naive B cells to secrete IgA1 and IgA2 as a consequence of isotype switching. The extracellular domain of CD40 binds with high affinity and high specificity to a ligand transiently expressed on activated T cells. This interaction of the CD40 antigen on B cells with its counter-structure on T cells represents a key step in T cell dependent B cell activation.