title: A novel IL-10-independent regulatory role for B cells in suppressing autoimmunity by maintenance of regulatory T cells via GITR ligand.
abstract: 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.
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53201-2178, USA.
authors.forename: Avijit
authors.initials: A
authors.lastname: Ray
authors.forename: Sreemanti
authors.initials: S
authors.lastname: Basu
authors.forename: Calvin B
authors.initials: CB
authors.lastname: Williams
authors.forename: Nita H
authors.initials: NH
authors.lastname: Salzman
authors.forename: Bonnie N
authors.initials: BN
authors.lastname: Dittel
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D060887:B7 Antigens / Q000276:immunology; D018920:Coculture Techniques; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D006706:Homeostasis; D016753:Interleukin-10 / Q000502:physiology; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000069283:Rituximab; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D048069:Tumor Necrosis Factors / Q000502:physiology*
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D060887:B7 Antigens; C556062:IL10 protein, mouse; C478966:Tnfsf18 protein, mouse; D048069:Tumor Necrosis Factors; D016753:Interleukin-10; D000069283:Rituximab