Article: article from journal or magazin.
The anti-apoptotic factor Bcl-2 can functionally substitute for the B cell survival but not for the marginal zone B cell differentiation activity of BAFF.
European Journal of Immunology
The TNF family ligand B cell-activating factor (BAFF, BLyS, TALL-1) is an essential factor for B cell development. BAFF binds to three receptors, BAFF-R, transmembrane activator and CAML interactor (TACI), and B cell maturation antigen (BCMA), but only BAFF-R is required for successful survival and maturation of splenic B cells. To test whether the effect of BAFF is due to the up-regulation of anti-apoptotic factors, TACI-Ig-transgenic mice, in which BAFF function is inhibited, were crossed with transgenic mice expressing FLICE-inhibitory protein (FLIP) or Bcl-2 in the B cell compartment. FLIP expression did not rescue B cells, while enforced Bcl-2 expression restored peripheral B cells and the ability to mount T-dependent antibody responses. However, many B cells retained immaturity markers and failed to express normal amounts of CD21. Marginal zone B cells were not restored and the T-independent IgG3, but not IgM, response was impaired in the TACI-IgxBcl-2 mice. These results suggest that BAFF is required not only to inhibit apoptosis of maturating B cells, but also to promote differentiation events, in particular those leading to the generation of marginal zone B cells.
Animals, Apoptosis/immunology, B-Cell Activating Factor, B-Lymphocytes/cytology, B-Lymphocytes/immunology, CASP8 and FADD-Like Apoptosis Regulating Protein, Carrier Proteins/genetics, Carrier Proteins/immunology, Cell Differentiation/immunology, Flow Cytometry, Gene Expression Regulation/immunology, Immunohistochemistry, Intracellular Signaling Peptides and Proteins, Membrane Proteins/immunology, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Transgenic, Proto-Oncogene Proteins c-bcl-2/genetics, Proto-Oncogene Proteins c-bcl-2/immunology, Spleen/immunology, Tumor Necrosis Factor-alpha/immunology
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