INTERLEUKIN-10 INDUCES B-LYMPHOCYTES FROM IGA-DEFICIENT PATIENTS TO SECRETE IGA

We have previously shown that human B lymphocytes cultured in the CD40 system, composed of an anti-CD40 mAb presented by a CD32-transfected fibroblastic cell line, proliferate hut do not secrete antibodies. How ever, the addition of particles of Staphylococcus aureus Cowan (SAC) i nduces B cell differentiation even in the absence of exogeneous cytoki nes (CD40/SAC system). Additionally, B lymphocytes cultured in the CD4 0 system in the presence of human IL-10, produce IgM, IgG, and IgA, an d Tg levels are further increased by SAC. Here, we have studied the ca pacity of peripheral blood lymphocytes from patients with IgA deficien cy (IgA-D) to secrete Igs, particularly IgA after CD40 triggering. Per ipheral blood mononuclear cells (PBMNC) from IgA-D patients cultured i n the CD40/SAC system produced IgM and IgG, but not IgA. The addition of IL-10 to the cultures, enhanced the production of IgM and IgG and m ost strikingly induced the production of high amounts of IgA. The addi tion of IL-10 to PBMNC from IgA-D patients activated through CD40 alon e resulted in the production of IgA. Thus, SAC and anti-CD40 mAb stimu late B cells to differentiate into cells secreting IgG and IgM whereas IL-10 plays a central role in inducing B cells from IgA-D patients to differentiate into IgA secreting cells.