Single-Cell Analysis of the Plasmablast Response to Vibrio cholerae Demonstrates Expansion of Cross-Reactive Memory B Cells
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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
Xu, Peng
Kováč, Pavol
Felgner, Phillip L.
Qadri, Firdausi
Wrammert, Jens
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1128/mBio.02021-16Metadata
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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.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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5181778/pdf/Terms of Use
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