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Overexpression of Bcl_XL in B Cells Promotes Th1 Response and Exacerbates Collagen-Induced Arthritis

Biao Zheng^*, Ekaterina Marinova^*, Kirsten Switzer^*, Daniel Wansley^*, Hongxia He^*, Roy Bheekha-Escura^*, Timothy W. Behrens and Shuhua Han^1,*

^* Department of Immunology, Baylor College of Medicine, Houston, TX 77030; and Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455

B cells play a pathogenic or regulatory role in many autoimmune diseases through production of autoantibodies, cytokine production, and Ag presentation. However, the mechanisms that regulate these B cell functions under different autoimmune settings remain unclear. In the current study, we found that when B cells overexpress an antiapoptotic gene, Bcl_XL, they significantly increased production of IFN- and enhanced Th1 response. Consistently, Bcl-x_L transgenic mice developed more severe and sustained collagen-induced arthritis due to the enhanced Th1 response. The production of autoantibodies in Bcl_XL transgenic mice was comparable to that in wild-type mice. Thus, our results indicate a novel role of Bcl_XL in regulating B cell functions and immune responses. In patients with rheumatoid arthritis, arthritogenic B cells often up-regulate Bcl_XL expression, which may not only render B cells resistant to apoptosis but also alter the ability of the autoreactive B cells to produce cytokines and modulate the inflammatory response. This may have therapeutic implications if Bcl_XL expression can be down-regulated in autoreactive B cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Address correspondence and reprint requests to Dr. Shuhua Han, Department of Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. E-mail address: shan{at}bcm.edu

² Abbreviations used in this paper: GC, germinal center; RA, rheumatoid arthritis; CIA, collagen-induced arthritis; CII, type II collagen; WT, wild type; DTH, delayed-type hypersensitivity; CGG, chicken -globulin; LN, lymph nodes.

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