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In small rodents, the natural reservoir species of this spirochete, infections lead to only modest disease manifestations, despite causing persistence infection. Although B cell responses are central for controlling bacterial tissue burden and disease manifestations, they lack classical aspects of T-dependent responses, such as sustained IgG affinity maturation and longevity, corresponding with a rapid collapse of germinal centers. Instead, the Ab response is characterized by strong and ongoing secretion of IgM, whose origins and impact on protective immunity to B. burgdorferi remain unknown. In this article, we demonstrate that B. burgdorferi infection\u2013induced IgM in mice was produced continuously, mainly by conventional B, not B-1 cells, in a T-independent manner. Although IgM was passively protective and restricted early bacteremia, its production had no effects on bacterial dissemination into solid tissues, nor did it affect Borrelia tissue burden. The latter was controlled by the induction of bactericidal IgG, as shown comparing infections in wild type mice with those of mice lacking exclusively secreted IgM\u2212\/\u2212, all class-switched Abs via deletion of aicda (AID\u2212\/\u2212), and all secreted Abs (secreted IgM\u2212\/\u2212 \u00d7 AID\u2212\/\u2212). Consistent with the notion that B. burgdorferi infection drives production of IgM over more tissue-penetrable IgG, we demonstrated increased short- and long-term IgM Ab responses also to a coadministered, unrelated Ag. Thus, the continued production of IgM may explain the absence of B. burgdorferi in the blood.<\/jats:p>","DOI":"10.4049\/jimmunol.2300384","type":"journal-article","created":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T12:21:57Z","timestamp":1696249317000},"page":"1540-1549","source":"Crossref","is-referenced-by-count":14,"title":["<i>Borrelia burgdorferi<\/i> Infection\u2013Induced Persistent IgM Secretion Controls Bacteremia, but Not Bacterial Dissemination or Tissue Burden"],"prefix":"10.1093","volume":"211","author":[{"given":"Christine J","family":"Hastey","sequence":"first","affiliation":[{"name":"Graduate Group in Microbiology, University of California Davis , Davis, CA"},{"name":"Center for Comparative Medicine, University of California Davis , Davis, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly J","family":"Olsen","sequence":"additional","affiliation":[{"name":"Center for Comparative Medicine, University of California Davis , Davis, CA"},{"name":"Department of Pathology, Microbiology & Immunology, School of Veterinary Medicine, University of California Davis , Davis, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5364-8060","authenticated-orcid":false,"given":"Rebecca A","family":"Elsner","sequence":"additional","affiliation":[{"name":"Graduate Group in Microbiology, University of California Davis , Davis, CA"},{"name":"Center for Comparative Medicine, University of California Davis , Davis, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4740-2467","authenticated-orcid":false,"given":"Sophia","family":"Mundigl","sequence":"additional","affiliation":[{"name":"Center for Comparative Medicine, University of California Davis , Davis, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0993-1672","authenticated-orcid":false,"given":"Giang Vu Vi","family":"Tran","sequence":"additional","affiliation":[{"name":"Center for Comparative Medicine, University of California Davis , Davis, CA"},{"name":"Department of Pathology, Microbiology & Immunology, School of Veterinary Medicine, University of California Davis , Davis, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen W","family":"Barthold","sequence":"additional","affiliation":[{"name":"Center for Comparative Medicine, University of California Davis , Davis, CA"},{"name":"Department of Pathology, Microbiology & Immunology, School of Veterinary Medicine, University of California Davis , Davis, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2891-4483","authenticated-orcid":false,"given":"Nicole","family":"Baumgarth","sequence":"additional","affiliation":[{"name":"Graduate Group in Microbiology, University of California Davis , Davis, CA"},{"name":"Center for Comparative Medicine, University of California Davis , Davis, CA"},{"name":"Department of Pathology, Microbiology & Immunology, School of Veterinary Medicine, University of California Davis , Davis, CA"},{"name":"Department of Molecular Microbiology and Immunology, Lyme and Tickborne Diseases Research and Education Institute, Johns Hopkins University , Baltimore, MD"},{"name":"Department of Molecular and Comparative Pathobiology, Johns Hopkins University , Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,10,2]]},"reference":[{"key":"2025020501012490700_r1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1056\/NEJM200107123450207","article-title":"Lyme disease","volume":"345","author":"Steere","year":"2001","journal-title":"N. 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