Interleukin-10 produced by B cells is crucial for the suppression of Th17/Th1 responses, induction of T regulatory type 1 cells and reduction of collagen-induced arthritis.
BACKGROUND
Interleukin-10 (IL-10) producing B cells, also known as regulatory B (Breg) cells, play a key role in controlling autoimmunity. Our laboratory and others have demonstrated a pivotal role for Bregs in rheumatological disorders, including experimental models of arthritis and lupus. The aim of this study was to identify the role of endogenous IL-10 secreting B cells in vivo in controlling the induction and disease progression of collagen-induced arthritis (CIA).


METHODS
We generated chimeric mice that had IL-10 knocked-out specifically in the B cell population. These mice were compared with wild-type (WT) B cell chimeric mice for their susceptibility to CIA.


RESULTS
Here we report that chimeric mice specifically lacking IL-10 producing B cells (IL-10-/- B cell) developed an exacerbated CIA compared to chimeric wild type B cell (WT B cell) mice. A marked increase in inflammatory Th1 and Th17 cells were detected in IL-10-/-B cell mice compared to WT B cell mice. Furthermore, there was a reduction in IL-10 secreting CD4+ Tr1 cells in these animals.


CONCLUSIONS
IL-10 producing B cells restrain inflammation by promoting differentiation of immuno-regulatory over pro-inflammatory T cells and, hence, act to maintain tolerance.
Centre for Rheumatology Research, Division of Medicine, University College London, Rayne Building, 5 University Street, London, WC1E 6JF, UK. Natalie.Carter@ucl.ac.uk
Natalie A
NA
Carter
Elizabeth C
EC
Rosser
Claudia
C
Mauri
D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17; D016753:Interleukin-10; D007371:Interferon-gamma