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B cell responses to purified polysaccharides are T cell independent and do not result in the formation of bona fide germinal centers, and the dominant Ab isotype produced during such responses is IgM with very few or no somatic mutations. Activation-induced cytidine deaminase (AID) is required for both somatic hypermutation and Ig isotype switching in humans and mice. To test the extent to which unmutated polysaccharide-specific IgM confers protective immunity, we immunized wildtype and AID\u2212\/\u2212 mice with either heat-killed Salmonella enterica serovar Typhi (S. Typhi) or purified Vi polysaccharide (ViPS). We found that wildtype and AID\u2212\/\u2212 mice immunized with heat-killed S. Typhi generated similar anti-ViPS IgM responses. As expected, wildtype, but not AID\u2212\/\u2212 mice generated ViPS-specific IgG. However, the differences in the Ab-dependent killing of S. Typhi mediated by the classical pathway of complement activation were not statistically significant. In ViPS-immunized wildtype and AID\u2212\/\u2212 mice, the ViPS-specific IgM levels and S. Typhi bactericidal Ab titers at 7 but not at 28 d postimmunization were also comparable. To test the protective immunity conferred by these immunizations, mice were challenged with a chimeric S. Typhimurium strain expressing ViPS. Compared with their naive counterparts, immunized wildtype and AID\u2212\/\u2212 mice exhibited significantly reduced bacterial burden regardless of the route of infection. These data indicate that an unmutated IgM response to ViPS contributes to protective immunity to S. Typhi.<\/jats:p>","DOI":"10.4049\/jimmunol.1701348","type":"journal-article","created":{"date-parts":[[2018,5,9]],"date-time":"2018-05-09T14:16:13Z","timestamp":1525875373000},"page":"4078-4084","source":"Crossref","is-referenced-by-count":17,"title":["An Unmutated IgM Response to the Vi Polysaccharide of <i>Salmonella<\/i> Typhi Contributes to Protective Immunity in a Murine Model of Typhoid"],"prefix":"10.1093","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3148-6846","authenticated-orcid":false,"given":"Kalgi D","family":"Pandya","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"Palomo-Caturla","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin A","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vijay K","family":"Sandilya","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhijiu","family":"Zhong","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Cancer Center, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kishore R","family":"Alugupalli","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia, PA 19107"},{"name":"Sidney Kimmel Cancer Center, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,6,15]]},"reference":[{"key":"2025030610152199600_r1","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1111\/j.1600-065X.2000.imr017518.x","article-title":"Terminal deoxynucleotidyl transferase and repertoire development","volume":"175","author":"Benedict","year":"2000","journal-title":"Immunol. 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