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Aberrant B cell repertoire selection associated with HIV neutralizing antibody breadth


A goal of HIV vaccine development is to elicit antibodies with neutralizing breadth. Broadly neutralizing antibodies (bNAbs) to HIV often have unusual sequences with long heavy-chain complementarity-determining region loops, high somatic mutation rates and polyreactivity. A subset of HIV-infected individuals develops such antibodies, but it is unclear whether this reflects systematic differences in their antibody repertoires or is a consequence of rare stochastic events involving individual clones. We sequenced antibody heavy-chain repertoires in a large cohort of HIV-infected individuals with bNAb responses or no neutralization breadth and uninfected controls, identifying consistent features of bNAb repertoires, encompassing thousands of B cell clones per individual, with correlated T cell phenotypes. These repertoire features were not observed during chronic cytomegalovirus infection in an independent cohort. Our data indicate that the development of numerous B cell lineages with antibody features associated with autoreactivity may be a key aspect in the development of HIV neutralizing antibody breadth.

Type Journal
ISBN 1529-2916 (Electronic) 1529-2908 (Linking)
Authors Roskin, K. M.; Jackson, K. J. L.; Lee, J. Y.; Hoh, R. A.; Joshi, S. A.; Hwang, K. K.; Bonsignori, M.; Pedroza-Pacheco, I.; Liao, H. X.; Moody, M. A.; Fire, A. Z.; Borrow, P.; Haynes, B. F.; Boyd, S. D.
Responsible Garvan Author Dr Katherine Jackson
Published Date 2020-02-01
Published Volume 21
Published Issue 2
Published Pages 199-209
Status Published in-print
DOI 10.1038/s41590-019-0581-0
URL link to publisher's version