The role of IL-10 and TGF-beta1 secretion by B lymphocytes in lupus prone mice

• Applicant: Dr. Lino Lars Teichmann
• Subject Area: Rheumatology
• Term: from 2009 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 108052102

B cells (B lymphocytes) play a major role in the pathogenesis of systemic lupus erythematosus and other autoimmune disorders. Efforts to understand the mechanisms by which B cells participate in the development and maintenance of autoimmune diseases have been boosted by the clinical success of B cell modulatory therapies. Recent studies indicate that similar to the situation with T cells not only pathogenic but also regulatory B cells (Bregs) are contained in the B cell compartment. The existence of Bregs could be demonstrated in murine models of rheumatoid arthritis, multiple sclerosis, diabetes mellitus type 1, inflammatory bowel disease and systemic lupus erythematosus. There is evidence that Bregs are particularly generated during B cell reconstitution after anti-CD20 mediated B cell depletion. The regulatory capacity of B cells has been ascribed to the secretion of the cytokines Interleukin 10 (IL-10) and Transforming growth factor β1 (TGF-β1). It stands to reason that activated B cells could be regulating T cells and themselves at the same time by the release of IL-10 and TGF-β1. We plan to test this hypothesis in a murine model of systemic lupus erythematosus (MRL/lpr) by B cell specific deletion of IL-10 or TGF-β1. Moreover, we will investigate whether Bregs can be induced by anti-CD20 mediated B cell depletion in MRL/lpr mice to establish Breg induction as a general mechanism of CD20 targeted therapy. We will conduct further experiments to shed light on the context in which Bregs secrete anti-inflammatory cytokines.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Mark J. Shlomchik, Ph.D.