Overexpression of Bcl(XL) in B cells promotes Th1 response and exacerbates collagen-induced arthritis.
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-gamma 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.
Zheng
Biao
B
Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
Marinova
Ekaterina
E
Switzer
Kirsten
K
Wansley
Daniel
D
He
Hongxia
H
Bheekha-Escura
Roy
R
Behrens
Timothy W
TW
Han
Shuhua
S
D000818:Animals; D000917:Antibody Formation; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D001323:Autoantibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy; D007371:Interferon-gamma / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D051020:bcl-X Protein / Q000235:genetics / Q000276:immunology*
D001323:Autoantibodies; C494812:Bcl2l1 protein, mouse; D051020:bcl-X Protein; D007371:Interferon-gamma