The effects of IFN-gamma on CD40-mediated activation of B cells from X-linked immunodeficient or normal mice
| Autor: | C Johnson-Léger, J Hasbold, M Holman, G G Klaus |
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| Rok vydání: | 1997 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 159:1150-1159 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.159.3.1150 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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