ACTIVATION OF THYMIC B-CELLS BY SIGNALS OF CD40 MOLECULES PLUS INTERLEUKIN-10

We have previously found that thymic B cells, particularly thymic CD5( +) B cells, show low responsiveness to the usual B cell stimulants suc h as lipopolysaccharide or anti-IgM plus interleukin (IL)-4, although they proliferate and produce antibodies after direct interaction with major histocompatibility complex class II-restricted T blasts. These f indings raise the possibility that a CD40-CD40 ligand (L) interaction is involved in the activation of thymic B cells. In the present study, we therefore examine this possibility using CD40L-transfected Chinese hamster ovary (CHO) cells or anti-CD40 monoclonal antibody (mAb). Whe n B cells in the spleen and peritoneal cavity were stimulated, they pr oliferated and produced immunoglobulin (Ig) in the presence of CD40L-C HO cells or anti-CD40 mAb alone. However, another signal delivered by IL-10 in addition to CD40L-CHO cells or anti-CD40 mAb was found to be necessary for thymic B cells to proliferate and secrete Ig. Other inte rleukins acting on B cells, such as IL-4, IL-5, and IL-6, had no effec t on the activation of thymic B cells, which thus have unique characte ristics not found in peripheral B cells. This report discusses the phy siological significance of IL-10- and CD40-driven signals in the activ ation of thymic B cells.