The effects of IFN-gamma on CD40-mediated activation of B cells from X-linked immunodeficient or normal mice.
B cell activation induced by cross-linking of CD40 is enhanced by costimulation with certain T cell-derived cytokines (generally Th2 type), most notably IL-4. We show here that the induction of DNA synthesis in normal mouse B cells by anti-CD40 mAb is also significantly enhanced by supernatants from anti-CD3-activated Th1 cells or from primary T cells. In both instances the costimulatory activity is specifically abrogated by neutralizing Abs against IFN-gamma. B cells from CBA/N immunodeficient (xid) mice are markedly hyporesponsive to most anti-CD40 Abs, even in the presence of IL-4. These cells do, however, synthesize DNA when stimulated by anti-CD40 plus supernatants from anti-CD3-stimulated primary T cells, by anti-CD40 plus IFN-gamma (but not IL-4), or by fixed, activated Th1 T cells. In all these instances, the mitogenic response of xid B cells is crucially dependent on the presence of IFN-gamma. This cytokine also enhanced CD40-induced homotypic adhesion of normal and xid B cells and potentiated CD40-mediated protection of B cells from spontaneous apoptosis. These data, therefore, indicate that IFN-gamma plays an essential role in the activation of B cells by Th1 T cells and by naive T cells during the initiation of primary Ab responses. The results with CBA/N B cells further suggest that the xid mutation selectively affects their capacity to respond to Th2-derived signals, for reasons that remain unclear.
Johnson-Léger
C
C
Division of Cellular Immunology, National Institute for Medical Research, London, United Kingdom.
Hasbold
J
J
Holman
M
M
Klaus
G G
GG
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051940:B7-2 Antigen; D017252:CD3 Complex / Q000502:physiology; D019013:CD40 Antigens / Q000276:immunology / Q000502:physiology*; D002448:Cell Adhesion / Q000276:immunology; D002474:Cell-Free System; D002478:Cells, Cultured; D005260:Female; D007153:Immunologic Deficiency Syndromes / Q000235:genetics; D007371:Interferon-gamma / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008211:Lymphocyte Cooperation; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology; D014960:X Chromosome / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051940:B7-2 Antigen; D017252:CD3 Complex; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins; D015847:Interleukin-4; D007371:Interferon-gamma