DIRECT HELPER T-CELL-INDUCED B-CELL DIFFERENTIATION INVOLVES INTERACTION BETWEEN T-CELL ANTIGEN-CD28 AND B-CELL ACTIVATION ANTIGEN-B7

Cognate interactions between major histocompatibility complex class II antigen (Ag)-reactive CD4+ T helper (T(h)) and Ag-presenting B cells induce first the activation of B cells and their subsequent differentiation into Ig-secreting cells (IgSC). The T(h) cell-associated homodimeric glycoprotein CD28 has been implicated as an important regulator of T(h) activation. Recently, B cell-associated early activation Ag B7 has been identified as a ligand for the CD28 molecule. In this study, we have examined using monoclonal antibodies (mAb) the roles of CD28 and B7 molecules during the T(h)-B cell cognate interactions leading to the differentiation of B7+ B cells. Anti-CD28 mAb 9.3 specifically inhibited proliferative responses of CD4+ T cells to both allogeneic B cells and soluble Ag-presenting autologous non-T cells. In addition, anti-CD28 mAb 9.3 inhibited T(h)-induced differentiation of alloantigen-presenting B cells into ISC. Similar inhibition of both Ag-induced T(h) activation and B cell differentiation into ISC was observed using mAb BB1 which recognizes a B cell-associated molecule B7. In contrast, non-cognate T(h)-independent exogenous interleukin 6-induced differentiation of B7+ B cells into ISC was not inhibited by mAb to either molecule. These results clearly demonstrate the involvement of CD28 on T(h) and its ligand B7 on B cells during cognate T(h)-B interactions leading to the differentiation of B cells. Furthermore, these results also suggest the development of new mAb-based therapeutic approaches for exaggerated B cell activation associated with certain autoimmune diseases such as systemic lupus erythematosus.