Suppressive functions of activated B cells in autoimmune diseases reveal the dual roles of Toll-like receptors in immunity.
B lymphocytes contribute to immunity through production of antibodies, antigen presentation to T cells, and secretion of cytokines. B cells are generally considered in autoimmune diseases as drivers of pathogenesis. This view is certainly justified, given the successful utilization of the B cell-depleting reagent rituximab in patients with rheumatoid arthritis or other autoimmune pathologies. In a number of cases, however, the depletion of B cells led to an exacerbation of symptoms in patients with autoimmune disorders. In a similar manner, mice lacking B cells can develop an aggravated course of disease in several autoimmune models. These paradoxical observations are now explained by the concept that activated B cells can suppress immune responses through the production of cytokines, especially interleukin-10. Here, we review the stimulatory signals that induce interleukin-10 secretion and suppressive functions in B cells and the phenotype of the B cells with such characteristics. Finally, we formulate a model explaining how this process of immune regulation by activated B cells can confer advantageous properties to the immune system in its combat with pathogens. Altogether, this review proposes that B-cell-mediated regulation is a fundamental property of the immune system, with features of great interest for the development of new cell-based therapies for autoimmune diseases.
Lampropoulou
Vicky
V
Laboratory of immune regulation, Deutsches Rheuma-Forschungszentrum, Berlin, Germany.
Calderon-Gomez
Elisabeth
E
Roch
Toralf
T
Neves
Patricia
P
Shen
Ping
P
Stervbo
Ulrik
U
Boudinot
Pierre
P
Anderton
Stephen M
SM
Fillatreau
Simon
S
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000628:therapy; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D010641:Phenotype; D015398:Signal Transduction / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology*
D051193:Toll-Like Receptors; D016753:Interleukin-10