IL-4 and anti-CD40 protect against Fas-mediated B cell apoptosis and induce B cell growth and differentiation.
Most Th2 clones, when activated, produce IL-4 and express CD40 ligand (CD40L) on their cell surface. Therefore, they can induce growth and differentiation of B cells by cognate help. In contrast, activated Th1 clones, which produce IFN-gamma and express both CD40L and Fas ligand (FasL) on their cell surface, often induce B cell apoptotic cell death. To understand the mechanism by which Th2 cells can induce B cell growth and differentiation in the presence of FasL-positive cells, we stimulated B cells with IL-4, anti-IgM and/or anti-CD40 in the presence of anti-Fas. We report here that addition of anti-Fas strongly inhibited anti-CD40-induced B cell proliferation without affecting anti-IgM-induced B cell proliferation. Furthermore we showed that stimulation of B cells with anti-CD40 induced the expression of Fas molecules on the B cells (approximately 30%) and rendered them highly sensitive to anti-Fas-mediated apoptotic cell death. Indeed, over 23% of anti-CD40-stimulated B cells showed hypodiploid DNA after being incubated with anti-Fas, while h2 cells could dominate over FasL-positive Th1 cells by production of CD40L and IL-4, which in combination induce antibody production and inhibit the Th1 cell-mediated immune response.
Nakanishi
K
K
Department of Immunology and Medical Zoology, Hyogo College of Medicine, Japan.
Matsui
K
K
Kashiwamura
S
S
Nishioka
Y
Y
Nomura
J
J
Nishimura
Y
Y
Sakaguchi
N
N
Yonehara
S
S
Higashino
K
K
Shinka
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D019013:CD40 Antigens / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D005260:Female; D015847:Interleukin-4 / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D019014:fas Receptor / Q000187:drug effects / Q000502:physiology*
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D019014:fas Receptor; D015847:Interleukin-4