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In particular, it has been suggested that infection\u2010induced stimulation of innate immune sensors can engage low affinity autoreactive B lymphocytes to mature and produce mutated IgG pathogenic autoantibodies. To test this hypothesis, we established a new knock\u2010in mouse model in which autoreactive B cells could be committed to an affinity maturation process. We show that a chronic bacterial infection allows the activation of such B cells and the production of nonmutated IgM autoantibodies. Moreover, in the constitutive presence of their soluble antigen, some autoreactive clones are able to acquire a germinal center phenotype, to induce <jats:italic>Aicda<\/jats:italic> gene expression and to introduce somatic mutations in the IgG heavy chain variable region on amino acids forming direct contacts with the autoantigen. Paradoxically, only lower affinity variants are detected, which strongly suggests that higher affinity autoantibodies secreting B cells are counterselected. For the first time, we demonstrate in vivo that a noncross\u2010reactive infectious agent can activate and induce autoreactive B cells to isotype switching and autoantigen\u2010driven mutations, but on a nonautoimmune background, tolerance mechanisms prevent the formation of consequently dangerous autoimmunity.<\/jats:p>","DOI":"10.1002\/eji.201545810","type":"journal-article","created":{"date-parts":[[2015,10,17]],"date-time":"2015-10-17T09:42:46Z","timestamp":1445074966000},"page":"131-146","source":"Crossref","is-referenced-by-count":7,"title":["Chronic bacterial infection activates autoreactive B cells and induces isotype switching and autoantigen\u2010driven mutations"],"prefix":"10.1002","volume":"46","author":[{"given":"Sophie","family":"Jung","sequence":"first","affiliation":[{"name":"CNRS UPR 3572 \u201cImmunopathology and Therapeutic Chemistry\u201d\/ Laboratory of Excellence Medalis Molecular and Cellular Biology Institute (IBMC)  Strasbourg France"},{"name":"\u201cP\u00f4le 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