Expression and function of TNF family member B cell-activating factor in the development of autoimmune arthritis.
B cell-activating factor (BAFF), a member of tumor necrosis factor family cytokines, has been shown to enhance the maturation and survival of peripheral B cells. While BAFF is implicated in regulating B cell function and autoimmunity, its role in the development of autoimmune arthritis has not been fully clarified. Using a collagen-induced arthritis (CIA) mouse model, we detected dysregulated expression of BAFF and its receptors in the peripheral lymphoid organs during arthritis induction. Elevated serum levels of BAFF were closely correlated with increased levels of anti-collagen antibodies during the CIA progression. Moreover, dendritic cells (DCs) and macrophages were found to express high amount of BAFF proteins at the acute and chronic stages of CIA, respectively. In cultures, recombinant BAFF suppressed apoptosis of splenic B cells from arthritic mice, and DC-induced B cell proliferation was specifically blocked by soluble decoy receptor B cell maturation antigen-Fc. These findings suggest that overproduction of BAFF by DCs and macrophages may play a crucial role in the pathogenesis of experimental arthritis.
Department of Pathology, The University of Hong Kong, Pokfulam Road, Hong Kong, The People's Republic of China .
Min
M
Zhang
King-Hung
KH
Ko
Queenie Lai Kwan
QL
Lam
Cherry Kam Chun
CK
Lo
Gopesh
G
Srivastava
Bojian
B
Zheng
Yu-Lung
YL
Lau
Liwei
L
Lu
D000818:Animals; D017209:Apoptosis; D001169:Arthritis, Experimental / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D001483:Base Sequence; D049109:Cell Proliferation; D003094:Collagen / Q000276:immunology; D018076:DNA, Complementary / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology; D015870:Gene Expression; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology*
D001323:Autoantibodies; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D018076:DNA, Complementary; D008565:Membrane Proteins; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; C486662:Tnfrsf13c protein, mouse; C505720:Tnfsf13b protein, mouse; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen