auf1 is involved in splenic follicular b cell maintenanceauf1参与脾滤泡b细胞的维护.pdfVIP

Sadri et al. BMC Immunology 2010, 11:1 /1471-2172/11/1 RESEARCH ARTICLE Open Access AUF1 is involved in splenic follicular B cell maintenance 1 1,2 1 1* Navid Sadri , Jin-Yu Lu , Michelle L Badura , Robert J Schneider Abstract Background: The adenosine/uridine-rich element (ARE)-binding protein AUF1 functions to regulate the inflammatory response through the targeted degradation of cytokine and other mRNAs that contain specific AREs in their 3’ noncoding region (3’ NCR). To investigate the role of AUF1 in the immune system, we characterized the lymphoid compartments of AUF1-deficient mice. Results: Mice lacking AUF1 exhibit an altered proportion and size of splenic B cell subsets. We show prominent apoptosis in splenic B cell follicles and reduced expression of Bcl-2, A1, and Bcl-XL correlate with increased turnover and significant reduction in the number and proportion of splenic FO B cells in AUF1-deficient mice. In addition, AUF1-deficient mice exhibit a sharp decrease in splenic size and lymphocyte cellularity. Bone marrow transfer studies demonstrate that AUF1 deficiency induces cell-autonomous defects in mature B cell subsets but not in the overall number of splenocytes. Reconstitution of irradiated adult AUF1-deficient mice with wild-type bone marrow restores the proportion of FO and marginal zone (MZ) B cells, but does not rescue the decrease in the number of splenocytes. Functionally, AUF1-deficient mice mount an attenuated response to T cell-independent (TI) antigen, which correlates with impaired MZ B cell function. Conclusion: These data indicate that AUF1 is important in the maintenance of splenic FO B cells and adequate humoral immune responses. Background m