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Susceptibility to Autoimmunity and B Cell Resistance to Apoptosis in Mice Lacking Androgen Receptor in B Cells
Biochemistry and Microbiology
  • Saleh Altuwaijri
  • Kuang-Hsiang Chuang
  • Kuo-Pao Lai
  • Jiann-Jyh Lai
  • Hung-Yun Lin
  • Faith M. Young
  • Andrea Bottaro
  • Meng-Yin Tsai
  • Wei-Ping Zeng, Marshall University
  • Hong-Chiang Chang
  • Shuyuan Yeh
  • Chawnshang Chang
Document Type
Article
Publication Date
4-1-2009
Abstract
Estrogens have been linked to a higher female incidence of autoimmune diseases. The role of androgen and the androgen receptor (AR) in autoimmune diseases, however, remains unclear. Here we report that the lack of AR in B cells in different strains of mice, namely general AR knockout, B cell-specific AR knockout, and naturally occurring testicular feminization mutation AR-mutant mice, as well as castrated wild-type mice, results in increased B cells in blood and bone marrow. Analysis of the targeted mice, together with bone marrow transplantation using Rag1 recipients, overexpression of retrovirally encoded AR-cDNA, and small interfering RNA-mediated AR mRNA knockdown approaches also show that the B cell expansion results from resistance to apoptosis and increased proliferation of bone marrow precursor B cells, accompanied by changes in several key modulators related to apoptosis, such as Fas/FasL signals, caspases -3 -8, nuclear factor -B, and Bcl-2. We also show that the effects of AR loss are, in part, B cell intrinsic. Mice bearing AR-deficient B cells show increased levels of serum IgG2a and IgG3 as well as basal double-stranded DNA-IgG antibodies and are more vulnerable to development of collagen-induced arthritis. Together, these data indicate that androgen/AR play a crucial role in B cell homeostasis and tolerance. Therapies targeting AR might provide an alternative strategy with which to battle autoimmune diseases.
Comments

This article first appeared in the April 2009 issue of Molecular Endocrinology, the member magazine of The Endocrine Society, and is reprinted with permission.

Copyright © 2012 The Endocrine Society

Citation Information
Altuwaijri S, Chuang KH, Lai KP, Lai JJ, Lin HY, Young FM, Bottaro A, Tsai MY, Zeng WP, Chang HC, Yeh S, Chang C. Susceptibility to Autoimmunity and B Cell Resistance to Apoptosis in Mice Lacking Androgen Receptor in B Cells. Mol Endocrinol. 2009 Apr;23(4): 444-53.