Single-Cell Analysis of the Plasmablast Response to Vibrio cholerae Demonstrates Expansion of Cross-Reactive Memory B Cells
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...
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American Society for Microbiology
2016-12-01
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doaj-91c47ff0bd504d36b32c7c58507e86ac2021-07-02T06:30:24ZengAmerican Society for MicrobiologymBio2150-75112016-12-0176e02021-1610.1128/mBio.02021-16Single-Cell Analysis of the Plasmablast Response to Vibrio cholerae Demonstrates Expansion of Cross-Reactive Memory B CellsRobert 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 KovááčStephen B. CalderwoodEdward T. RyanPhillip L. FelgnerFirdausi QadriJens WrammertJason B. HarrisWe 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.http://mbio.asm.org/cgi/content/full/7/6/e02021-16 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
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 Kovááč Stephen B. Calderwood Edward T. Ryan Phillip L. Felgner Firdausi Qadri Jens Wrammert Jason B. Harris |
spellingShingle |
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 Kovááč Stephen B. Calderwood Edward T. Ryan Phillip L. Felgner Firdausi Qadri Jens Wrammert Jason B. Harris Single-Cell Analysis of the Plasmablast Response to Vibrio cholerae Demonstrates Expansion of Cross-Reactive Memory B Cells mBio |
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 Kovááč 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 Vibrio cholerae Demonstrates Expansion of Cross-Reactive Memory B Cells |
title_short |
Single-Cell Analysis of the Plasmablast Response to Vibrio cholerae Demonstrates Expansion of Cross-Reactive Memory B Cells |
title_full |
Single-Cell Analysis of the Plasmablast Response to Vibrio cholerae Demonstrates Expansion of Cross-Reactive Memory B Cells |
title_fullStr |
Single-Cell Analysis of the Plasmablast Response to Vibrio cholerae Demonstrates Expansion of Cross-Reactive Memory B Cells |
title_full_unstemmed |
Single-Cell Analysis of the Plasmablast Response to Vibrio cholerae Demonstrates Expansion of Cross-Reactive Memory B Cells |
title_sort |
single-cell analysis of the plasmablast response to vibrio cholerae demonstrates expansion of cross-reactive memory b cells |
publisher |
American Society for Microbiology |
series |
mBio |
issn |
2150-7511 |
publishDate |
2016-12-01 |
description |
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. |
url |
http://mbio.asm.org/cgi/content/full/7/6/e02021-16 |
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