Single-Cell Analysis of the Plasmablast Response to <named-content content-type="genus-species">Vibrio cholerae</named-content> Demonstrates Expansion of Cross-Reactive Memory B Cells
ABSTRACT We characterized the acute B cell response in adults with cholera by analyzing the repertoire, specificity, and functional characteristics of 138 monoclonal antibodies (MAbs) generated from single-cell-sorted plasmablasts. We found that the cholera-induced responses were characterized by hi...
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American Society for Microbiology
2016
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oai:doaj.org-article:545c93248a4d4ab2b5a66d76c072274b2021-11-15T15:50:16ZSingle-Cell Analysis of the Plasmablast Response to <named-content content-type="genus-species">Vibrio cholerae</named-content> Demonstrates Expansion of Cross-Reactive Memory B Cells10.1128/mBio.02021-162150-7511https://doaj.org/article/545c93248a4d4ab2b5a66d76c072274b2016-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02021-16https://doaj.org/toc/2150-7511ABSTRACT We characterized the acute B cell response in adults with cholera by analyzing the repertoire, specificity, and functional characteristics of 138 monoclonal antibodies (MAbs) generated from single-cell-sorted plasmablasts. We found that the cholera-induced responses were characterized by high levels of somatic hypermutation and large clonal expansions. A majority of the expansions targeted cholera toxin (CT) or lipopolysaccharide (LPS). Using a novel proteomics approach, we were able to identify sialidase as another major antigen targeted by the antibody response to Vibrio cholerae infection. Antitoxin MAbs targeted both the A and B subunits, and most were also potent neutralizers of enterotoxigenic Escherichia coli heat-labile toxin. LPS-specific MAbs uniformly targeted the O-specific polysaccharide, with no detectable responses to either the core or the lipid moiety of LPS. Interestingly, the LPS-specific antibodies varied widely in serotype specificity and functional characteristics. One participant infected with the Ogawa serotype produced highly mutated LPS-specific antibodies that preferentially bound the previously circulating Inaba serotype. This demonstrates durable memory against a polysaccharide antigen presented at the mucosal surface and provides a mechanism for the long-term, partial heterotypic immunity seen following cholera. IMPORTANCE Cholera is a diarrheal disease that results in significant mortality. While oral cholera vaccines are beneficial, they do not achieve equivalent protection compared to infection with Vibrio cholerae. Although antibodies likely mediate protection, the mechanisms of immunity following cholera are poorly understood, and a detailed understanding of antibody responses to cholera is of significance for human health. In this study, we characterized the human response to cholera at the single-plasmablast, monoclonal antibody level. Although this approach has not been widely applied to the study of human bacterial infection, we were able to uncover the basis of cross-reactivity between different V. cholerae serotypes and the likely impact of prior enterotoxigenic Escherichia coli exposure on the response to cholera, as well as identify novel antigenic targets. In addition to improving our understanding of the repertoire and function of the antibody response to cholera in humans, this study has implications for future cholera vaccination efforts.Robert C. KauffmanTaufiqur R. BhuiyanRie NakajimaLeslie M. Mayo-SmithRasheduzzaman RashuMohammad Rubel HoqFahima ChowdhuryAshraful Islam KhanAtiqur RahmanSiddhartha K. BhaumikLevelle HarrisJustin T. O'NealJessica F. TrostNur Haq AlamAlgis JasinskasEmmanuel DotseyMeagan KellyRichelle C. CharlesPeng XuPavol KováčStephen B. CalderwoodEdward T. RyanPhillip L. FelgnerFirdausi QadriJens WrammertJason B. HarrisAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 6 (2016) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Microbiology QR1-502 |
| spellingShingle |
Microbiology QR1-502 Robert C. Kauffman Taufiqur R. Bhuiyan Rie Nakajima Leslie M. Mayo-Smith Rasheduzzaman Rashu Mohammad Rubel Hoq Fahima Chowdhury Ashraful Islam Khan Atiqur Rahman Siddhartha K. Bhaumik Levelle Harris Justin T. O'Neal Jessica F. Trost Nur Haq Alam Algis Jasinskas Emmanuel Dotsey Meagan Kelly Richelle C. Charles Peng Xu Pavol Kováč Stephen B. Calderwood Edward T. Ryan Phillip L. Felgner Firdausi Qadri Jens Wrammert Jason B. Harris Single-Cell Analysis of the Plasmablast Response to <named-content content-type="genus-species">Vibrio cholerae</named-content> Demonstrates Expansion of Cross-Reactive Memory B Cells |
| description |
ABSTRACT We characterized the acute B cell response in adults with cholera by analyzing the repertoire, specificity, and functional characteristics of 138 monoclonal antibodies (MAbs) generated from single-cell-sorted plasmablasts. We found that the cholera-induced responses were characterized by high levels of somatic hypermutation and large clonal expansions. A majority of the expansions targeted cholera toxin (CT) or lipopolysaccharide (LPS). Using a novel proteomics approach, we were able to identify sialidase as another major antigen targeted by the antibody response to Vibrio cholerae infection. Antitoxin MAbs targeted both the A and B subunits, and most were also potent neutralizers of enterotoxigenic Escherichia coli heat-labile toxin. LPS-specific MAbs uniformly targeted the O-specific polysaccharide, with no detectable responses to either the core or the lipid moiety of LPS. Interestingly, the LPS-specific antibodies varied widely in serotype specificity and functional characteristics. One participant infected with the Ogawa serotype produced highly mutated LPS-specific antibodies that preferentially bound the previously circulating Inaba serotype. This demonstrates durable memory against a polysaccharide antigen presented at the mucosal surface and provides a mechanism for the long-term, partial heterotypic immunity seen following cholera. IMPORTANCE Cholera is a diarrheal disease that results in significant mortality. While oral cholera vaccines are beneficial, they do not achieve equivalent protection compared to infection with Vibrio cholerae. Although antibodies likely mediate protection, the mechanisms of immunity following cholera are poorly understood, and a detailed understanding of antibody responses to cholera is of significance for human health. In this study, we characterized the human response to cholera at the single-plasmablast, monoclonal antibody level. Although this approach has not been widely applied to the study of human bacterial infection, we were able to uncover the basis of cross-reactivity between different V. cholerae serotypes and the likely impact of prior enterotoxigenic Escherichia coli exposure on the response to cholera, as well as identify novel antigenic targets. In addition to improving our understanding of the repertoire and function of the antibody response to cholera in humans, this study has implications for future cholera vaccination efforts. |
| format |
article |
| author |
Robert C. Kauffman Taufiqur R. Bhuiyan Rie Nakajima Leslie M. Mayo-Smith Rasheduzzaman Rashu Mohammad Rubel Hoq Fahima Chowdhury Ashraful Islam Khan Atiqur Rahman Siddhartha K. Bhaumik Levelle Harris Justin T. O'Neal Jessica F. Trost Nur Haq Alam Algis Jasinskas Emmanuel Dotsey Meagan Kelly Richelle C. Charles Peng Xu Pavol Kováč Stephen B. Calderwood Edward T. Ryan Phillip L. Felgner Firdausi Qadri Jens Wrammert Jason B. Harris |
| author_facet |
Robert C. Kauffman Taufiqur R. Bhuiyan Rie Nakajima Leslie M. Mayo-Smith Rasheduzzaman Rashu Mohammad Rubel Hoq Fahima Chowdhury Ashraful Islam Khan Atiqur Rahman Siddhartha K. Bhaumik Levelle Harris Justin T. O'Neal Jessica F. Trost Nur Haq Alam Algis Jasinskas Emmanuel Dotsey Meagan Kelly Richelle C. Charles Peng Xu Pavol Kováč Stephen B. Calderwood Edward T. Ryan Phillip L. Felgner Firdausi Qadri Jens Wrammert Jason B. Harris |
| author_sort |
Robert C. Kauffman |
| title |
Single-Cell Analysis of the Plasmablast Response to <named-content content-type="genus-species">Vibrio cholerae</named-content> Demonstrates Expansion of Cross-Reactive Memory B Cells |
| title_short |
Single-Cell Analysis of the Plasmablast Response to <named-content content-type="genus-species">Vibrio cholerae</named-content> Demonstrates Expansion of Cross-Reactive Memory B Cells |
| title_full |
Single-Cell Analysis of the Plasmablast Response to <named-content content-type="genus-species">Vibrio cholerae</named-content> Demonstrates Expansion of Cross-Reactive Memory B Cells |
| title_fullStr |
Single-Cell Analysis of the Plasmablast Response to <named-content content-type="genus-species">Vibrio cholerae</named-content> Demonstrates Expansion of Cross-Reactive Memory B Cells |
| title_full_unstemmed |
Single-Cell Analysis of the Plasmablast Response to <named-content content-type="genus-species">Vibrio cholerae</named-content> Demonstrates Expansion of Cross-Reactive Memory B Cells |
| title_sort |
single-cell analysis of the plasmablast response to <named-content content-type="genus-species">vibrio cholerae</named-content> demonstrates expansion of cross-reactive memory b cells |
| publisher |
American Society for Microbiology |
| publishDate |
2016 |
| url |
https://doaj.org/article/545c93248a4d4ab2b5a66d76c072274b |
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