IFN-alpha/beta enhances BCR-dependent B cell responses.
Type I interferon (IFN-I) is constitutively produced in the bone marrow (BM), and induced at sites of inflammation and following infection by viruses or microorganisms. We have previously shown that IFN-I regulates the generation and selection of normal B cell populations in the BM. In the present work, we assess the effects of IFN-I on mature B cell function by monitoring the responses of IFN-alpha/beta-treated murine splenic B cells to apoptotic, mitogenic and activating stimuli. A similar analysis is performed on BM mature B cells obtained from wild-type or IFN-I receptor-deficient mice. IFN-alpha/beta is shown to induce B cells to a state of partial activation characterized by the up-regulation of CD69, CD86 and CD25 molecules in the absence of either proliferation or terminal differentiation. B cells treated with IFN-alpha/beta show an increased survival and resistance to Fas-mediated apoptosis. IFN-alpha/beta also enhances B cell responses to BCR ligation such as calcium fluxes, IgM internalization, induction of activation markers and proliferation. These results indicate that in addition to its inhibitory effect on viral replication and T cell apoptosis, IFN-alpha/beta plays an essential role during an inflammatory response by lowering the threshold for B cell induction, thereby promoting fast and polyclonal antibody responses.
Braun
Déborah
D
Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, 2781 Oeiras, Portugal.
Caramalho
Iris
I
Demengeot
Jocelyne
J
D000818:Animals; D000954:Antigens, Surface / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D007370:Interferon Type I / Q000378:metabolism / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D011956:Receptors, Cell Surface; D015398:Signal Transduction
D000954:Antigens, Surface; D007370:Interferon Type I; D011947:Receptors, Antigen, B-Cell; D011956:Receptors, Cell Surface