| Autor: |
Kalgi D, Pandya, Isabel, Palomo-Caturla, Justin A, Walker, Vijay, K Sandilya, Zhijiu, Zhong, Kishore R, Alugupalli |
| Rok vydání: |
2017 |
| Předmět: |
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| Zdroj: |
Journal of immunology (Baltimore, Md. : 1950). 200(12) |
| ISSN: |
1550-6606 |
| Popis: |
T cell-dependent B cell responses typically develop in germinal centers. Antibodies generated during such responses are isotype-switched and high-affinity to the antigen due to somatic hypermutation of antibody genes. B cell responses to purified polysaccharides are T cell-independent, do not result in the formation of bona fide germinal centers, and the dominant antibody 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(−/−) mice with either heat-killed Salmonella enterica serovar Typhi (S. Typhi) or purified Vi polysaccharide (ViPS). We found that wildtype and AID(−/−) mice immunized with heat-killed S. Typhi generated similar anti-ViPS IgM responses. As expected, wildtype but not AID(−/−) mice generated ViPS-specific IgG. However, the differences in the antibody-dependent killing of S. Typhi mediated by the classical pathway of complement activation were not statistically significant. In ViPS-immunized wildtype and AID(−/−) mice the ViPS-specific IgM levels and S. Typhi bactericidal antibody titers at 7, but not at 28 days post-immunization were also comparable. To test the protective immunity conferred by these immunizations, mice were challenged with a chimeric S. Typhimurium strain expressing ViPS. Compared to their naïve counterparts, immunized wildtype and AID(−/−) 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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