Single-Cell Analysis of the Plasmablast Response to Vibrio cholerae Demonstrates Expansion of Cross-Reactive Memory B Cells

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Single-Cell Analysis of the Plasmablast Response to Vibrio cholerae Demonstrates Expansion of Cross-Reactive Memory B Cells

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Title: Single-Cell Analysis of the Plasmablast Response to Vibrio cholerae Demonstrates Expansion of Cross-Reactive Memory B Cells
Author: Kauffman, Robert C.; Bhuiyan, Taufiqur R.; Nakajima, Rie; Mayo-Smith, Leslie M.; Rashu, Rasheduzzaman; Hoq, Mohammad Rubel; Chowdhury, Fahima; Khan, Ashraful Islam; Rahman, Atiqur; Bhaumik, Siddhartha K.; Harris, Levelle; O'Neal, Justin T.; Trost, Jessica F.; Alam, Nur Haq; Jasinskas, Algis; Dotsey, Emmanuel; Kelly, Meagan; Charles, Richelle C.; Xu, Peng; Kováč, Pavol; Calderwood, Stephen B.; Ryan, Edward T.; Felgner, Phillip L.; Qadri, Firdausi; Wrammert, Jens; Harris, Jason B.

Note: Order does not necessarily reflect citation order of authors.

Citation: Kauffman, R. C., T. R. Bhuiyan, R. Nakajima, L. M. Mayo-Smith, R. Rashu, M. R. Hoq, F. Chowdhury, et al. 2016. “Single-Cell Analysis of the Plasmablast Response to Vibrio cholerae Demonstrates Expansion of Cross-Reactive Memory B Cells.” mBio 7 (6): e02021-16. doi:10.1128/mBio.02021-16. http://dx.doi.org/10.1128/mBio.02021-16.
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Abstract: 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.
Published Version: doi:10.1128/mBio.02021-16
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5181778/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:29739189
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