Suppressive functions of activated B cells in autoimmune diseases reveal the dual roles of Toll-like receptors in immunity
Vicky Lampropoulou,
Elisabeth Calderon-Gomez,
Toralf Roch,
Patricia Neves,
Ping Shen,
Ulrik Stervbo,
Pierre Boudinot,
Stephen M. Anderton,
Simon Fillatreau,
Vicky Lampropoulou
Laboratory of immune regulation, Deutsches Rheuma-Forschungszentrum, Berlin, Germany.
Search for more papers by this authorElisabeth Calderon-Gomez
Laboratory of immune regulation, Deutsches Rheuma-Forschungszentrum, Berlin, Germany.
Search for more papers by this authorToralf Roch
Laboratory of immune regulation, Deutsches Rheuma-Forschungszentrum, Berlin, Germany.
Search for more papers by this authorPatricia Neves
Laboratory of immune regulation, Deutsches Rheuma-Forschungszentrum, Berlin, Germany.
Search for more papers by this authorPing Shen
Laboratory of immune regulation, Deutsches Rheuma-Forschungszentrum, Berlin, Germany.
Search for more papers by this authorUlrik Stervbo
Laboratory of immune regulation, Deutsches Rheuma-Forschungszentrum, Berlin, Germany.
Search for more papers by this authorPierre Boudinot
Virologie et Immunologie Moléculaires, INRA, Jouy-en-Josas, France.
Search for more papers by this authorStephen M. Anderton
Centre for Inflammation Research and Centre for Multiple Sclerosis Research, Queen’s Medical research Institute, University of Edinburgh, Edinburgh, United Kingdom.
Search for more papers by this authorSimon Fillatreau
Laboratory of immune regulation, Deutsches Rheuma-Forschungszentrum, Berlin, Germany.
Search for more papers by this authorVicky Lampropoulou,
Elisabeth Calderon-Gomez,
Toralf Roch,
Patricia Neves,
Ping Shen,
Ulrik Stervbo,
Pierre Boudinot,
Stephen M. Anderton,
Simon Fillatreau,
Vicky Lampropoulou
Laboratory of immune regulation, Deutsches Rheuma-Forschungszentrum, Berlin, Germany.
Search for more papers by this authorElisabeth Calderon-Gomez
Laboratory of immune regulation, Deutsches Rheuma-Forschungszentrum, Berlin, Germany.
Search for more papers by this authorToralf Roch
Laboratory of immune regulation, Deutsches Rheuma-Forschungszentrum, Berlin, Germany.
Search for more papers by this authorPatricia Neves
Laboratory of immune regulation, Deutsches Rheuma-Forschungszentrum, Berlin, Germany.
Search for more papers by this authorPing Shen
Laboratory of immune regulation, Deutsches Rheuma-Forschungszentrum, Berlin, Germany.
Search for more papers by this authorUlrik Stervbo
Laboratory of immune regulation, Deutsches Rheuma-Forschungszentrum, Berlin, Germany.
Search for more papers by this authorPierre Boudinot
Virologie et Immunologie Moléculaires, INRA, Jouy-en-Josas, France.
Search for more papers by this authorStephen M. Anderton
Centre for Inflammation Research and Centre for Multiple Sclerosis Research, Queen’s Medical research Institute, University of Edinburgh, Edinburgh, United Kingdom.
Search for more papers by this authorSimon Fillatreau
Laboratory of immune regulation, Deutsches Rheuma-Forschungszentrum, Berlin, Germany.
Search for more papers by this authorS. Fillatreau
Deutsches Rheuma-ForschungszentrumChariteplatz 110117 BerlinGermanyTel.: +49 0 30 284 60 752Fax: +49 0 30 284 60 603e-mail: [email protected]
Abstract
Summary: 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.
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