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The most well studied are the anti\u2010nuclear antibody responses characteristic of systemic lupus erythematosus and studies over the past decade or so have demonstrated a critical role for signaling by TLR7 and\/or TLR9 in B cells to promote these responses. These Toll\u2010like receptors (TLRs) can promote T\u2010cell\u2010independent extrafollicular antibody responses with a heavy\u2010chain class switch and a low degree of somatic mutation, but they can also strongly boost the germinal center response that gives rise to high\u2010affinity antibodies and long\u2010lived plasma cells. TLRs have been shown to enhance affinity maturation in germinal center responses to produce high\u2010affinity neutralizing antibodies in several virus infection models of mice. Although more data are needed, it appears that anti\u2010nuclear antibodies in mouse models of lupus and in lupus patients can be generated by either pathway, provided there are genetic susceptibility alleles that compromise B\u2010cell tolerance at one or another stage. Limited data in other autoimmune diseases suggest that the germinal center response may be the predominant pathway leading to autoantibodies in those diseases. A better understanding of the mechanisms of autoantibody production may ultimately be helpful in the development of targeted therapeutics for lupus or other autoimmune diseases.<\/jats:p>","DOI":"10.1038\/icb.2016.78","type":"journal-article","created":{"date-parts":[[2016,8,26]],"date-time":"2016-08-26T08:21:18Z","timestamp":1472199678000},"page":"918-924","source":"Crossref","is-referenced-by-count":35,"title":["Germinal centers and autoimmune disease in humans and mice"],"prefix":"10.1111","volume":"94","author":[{"given":"Anthony L","family":"DeFranco","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of California  San Francisco CA 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