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Castigli, E, Scott, S, Dedeoglu, F, Bryce, P, Jabara, H, Bhan, AK, Mizoguchi, E and Geha, RS (2004) Impaired IgA class switching in APRIL-deficient mice. Proc. Natl. Acad. Sci. U.S.A. 101:3903-8


The tumor necrosis factor (TNF) family member APRIL binds to the receptors BCMA on B cells and TACI on B and T cells. To investigate the role of APRIL in immunity, we generated APRIL-deficient mice. APRIL(-/-) mice have normal T and B lymphocyte development, normal T and B cell proliferation in vitro, but increased numbers of CD44(hi)CD62L(lo) CD4(+) effector/memory T cells and increased IgG responses to T-dependent antigens. Serum IgA levels were significantly decreased, and serum IgA antibody responses to mucosal immunization with TD antigens and to type 1 T-independent antigens were impaired in APRIL(-/-) mice. APRIL by itself induced IgA as well as IgG1 isotype switching in CD40-deficient IgM(+)IgD(+) sorted B cells. These results suggest that APRIL down-regulates T cell-dependent antibody responses and promotes IgA class switching.


PubMed PMC374342 Online version:10.1073/pnas.0307348101


Animals; Antigens/immunology; Cell Division/immunology; Cell Division/physiology; Humans; Immunoglobulin A/blood; Immunoglobulin A/immunology; Immunoglobulin A/physiology; Immunoglobulin Class Switching/immunology; Immunoglobulin Class Switching/physiology; Lymphocytes/immunology; Lymphocytes/physiology; Lymphoid Tissue; Mice; Mice, Transgenic; Mutation; Neuropeptides/deficiency; Neuropeptides/genetics; Neuropeptides/physiology; Nuclear Proteins/deficiency; Nuclear Proteins/genetics; Nuclear Proteins/physiology; Reverse Transcriptase Polymerase Chain Reaction



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