A novel IL-10-independent regulatory role for B cells in suppressing autoimmunity by maintenance of regulatory T cells via GITR ligand.

Authors:
Avijit Ray, PhD
Avijit Ray, PhD
AbbVie
Senior Scientist II
Immunology, Immuno-oncology, Autoimmunity and Inflammation, Immune tolerance
North Chicago, IL | United States
Sreemanti Basu
Sreemanti Basu
Blood Research Institute
United States
Calvin B Williams
Calvin B Williams
Medical College of Wisconsin
United States
Nita H Salzman
Nita H Salzman
Medical College of Wisconsin
United States
Bonnie N Dittel
Bonnie N Dittel
Blood Research Institute

J Immunol 2012 Apr 24;188(7):3188-98. Epub 2012 Feb 24.

Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53201-2178, USA.

B cells are important for the regulation of autoimmune responses. In experimental autoimmune encephalomyelitis (EAE), B cells are required for spontaneous recovery in acute models. Production of IL-10 by regulatory B cells has been shown to modulate the severity EAE and other autoimmune diseases. Previously, we suggested that B cells regulated the number of CD4(+)Foxp3(+) T regulatory cells (Treg) in the CNS during EAE. Because Treg suppress autoimmune responses, we asked whether B cells control autoimmunity by maintenance of Treg numbers. B cell deficiency achieved either genetically (μMT) or by depletion with anti-CD20 resulted in a significant reduction in the number of peripheral but not thymic Treg. Adoptive transfer of WT B cells into μMT mice restored both Treg numbers and recovery from EAE. When we investigated the mechanism whereby B cells induce the proliferation of Treg and EAE recovery, we found that glucocorticoid-induced TNF ligand, but not IL-10, expression by B cells was required. Of clinical significance is the finding that anti-CD20 depletion of B cells accelerated spontaneous EAE and colitis. Our results demonstrate that B cells play a major role in immune tolerance required for the prevention of autoimmunity by maintenance of Treg via their expression of glucocorticoid-induced TNFR ligand.

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Source
http://dx.doi.org/10.4049/jimmunol.1103354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3311743PMC

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April 2012
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