Direct helper T cell‐induced B cell differentiation involves interaction between T cell antigen CD28 and B cell activation antigen B7

Abstract

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.