AUF1 is involved in splenic follicular B cell maintenance

BMC Immunology

Research Article

Robert J Schneider¹  Navid Sadri¹  Michelle L Badura¹  Jin-Yu Lu² 

[1] Department of Microbiology, New York University School of Medicine, 550 First Avenue, 10016, New York, NY, USA;Department of Microbiology, New York University School of Medicine, 550 First Avenue, 10016, New York, NY, USA;BCMM 231, Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Ave, 06536, New Haven, CT, USA;

关键词: Germinal Center;    Marginal Zone;    Splenic Lymphocyte;    Class Switch Recombination;    CD40 Engagement;   

DOI  :  10.1186/1471-2172-11-1

 received in 2009-04-30, accepted in 2010-01-11,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe 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.ResultsMice 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.ConclusionThese data indicate that AUF1 is important in the maintenance of splenic FO B cells and adequate humoral immune responses.

【 授权许可】

Unknown   
© Sadri et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.