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B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6–producing B cells

Authors :
Barr, Tom A.
Shen, Ping
Brown, Sheila
Lampropoulou, Vicky
Roch, Toralf
Lawrie, Sarah
Fan, Boli
O’Connor, Richard A.
Anderton, Stephen M.
Bar-Or, Amit
Fillatreau, Simon
Gray, David
Source :
The Journal of Experimental Medicine; May 2012, Vol. 209 Issue: 5 p1001-1010, 10p
Publication Year :
2012

Abstract

B cells have paradoxical roles in autoimmunity, exerting both pathogenic and protective effects. Pathogenesis may be antibody independent, as B cell depletion therapy (BCDT) leads to amelioration of disease irrespective of autoantibody ablation. However, the mechanisms of pathogenesis are poorly understood. We demonstrate that BCDT alleviates central nervous system autoimmunity through ablation of IL-6–secreting pathogenic B cells. B cells from mice with experimental autoimmune encephalomyelitis (EAE) secreted elevated levels of IL-6 compared with B cells from naive controls, and mice with a B cell–specific IL-6 deficiency showed less severe disease than mice with wild-type B cells. Moreover, BCDT ameliorated EAE only in mice with IL-6–sufficient B cells. This mechanism of pathogenesis may also operate in multiple sclerosis (MS) because B cells from MS patients produced more IL-6 than B cells from healthy controls, and this abnormality was normalized with B cell reconstitution after Rituximab treatment. This suggests that BCDT improved disease progression, at least partly, by eliminating IL-6–producing B cells in MS patients. Taking these data together, we conclude that IL-6 secretion is a major mechanism of B cell–driven pathogenesis in T cell–mediated autoimmune disease such as EAE and MS.

Details

Language :
English
ISSN :
00221007 and 15409538
Volume :
209
Issue :
5
Database :
Supplemental Index
Journal :
The Journal of Experimental Medicine
Publication Type :
Periodical
Accession number :
ejs27413761
Full Text :
https://doi.org/10.1084/jem.20111675