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 but do not secrete immunoglobulins (Igs). However, the addition of particles of Staphylococcus aureus Co wan (SAG) induces B cell to secrete considerable amounts of Igs even i n the absence of exogeneous cytokines (CD40/SAC system). Additionally, B lymphocytes cultured in the CD40 system in the presence of human IL -10, produce high level of IgM, IgG and IgA, which are further increas ed by addition of SAG. Here, we have studied the capacity of periphera l blood lymphocytes from patients with IgA deficiency (ISA-D) to secre te Igs, particularly IgA after CD40 triggering. Peripheral blood monon uclear cells (PBMNC) from IgA-D patients cultured in the CD40/SAC syst em produced IgM and IgG, but no IgA. The addition of IL-10 to the cult ures, enhanced the production of IgM and IgG and most strikingly induc ed the production of high amounts of IgA. The addition of IL-10 to PBM NC from ISA-D patients activated through CD40 alone resulted in the pr oduction of IgA. Thus, IL-10 can remove the block in B cell differenti ation and allows B cells from IgA-D patients to differentiate into IgA secreting cells.