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 (Th) and Ag-presenting B cells induce first the activation of B cells and their subsequent differentiation into Ig-secreting cells (IgSC). The Th cell-associated homodimeric glycoprotein CD28 has been implicated as an important regulator of Th 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 Th-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 Th-induced differentiation of alloantigen-presenting B cells into ISC. Similar inhibition of both Ag-induced Th activation and B cell differentiation into ISC was observed using mAb BB1 which recognizes a B cell-associated molecule B7. In contrast, non-cognate Th-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 Th and its ligand B7 on B cells during cognate Th-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.
Damle
N K
NK
Oncogen Division, Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121.
Linsley
P S
PS
Ledbetter
J A
JA
D015703:Antigens, CD / Q000502:physiology*; D000943:Antigens, Differentiation / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology*; D018106:CD28 Antigens; D015704:CD4 Antigens / Q000032:analysis; D002450:Cell Communication; D002454:Cell Differentiation; D015793:HLA-B7 Antigen / Q000502:physiology*; D006649:Histocompatibility Antigens / Q000032:analysis; D006801:Humans; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D015704:CD4 Antigens; D015793:HLA-B7 Antigen; D006649:Histocompatibility Antigens; D017493:Leukocyte Common Antigens