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High-affinity memory B cells induced by conjugate vaccines against weak tumor antigens are vulnerable to nonconjugated antigen

Savelyeva, Natalia, Shipton, Michael, Suchacki, Amy, Babbage, Gavin and Stevenson, Freda K. (2011) High-affinity memory B cells induced by conjugate vaccines against weak tumor antigens are vulnerable to nonconjugated antigen Blood, 118, (3), pp. 650-659. (doi:10.1182/blood-2011-01-328864). (PMID:21613251).

Record type: Article

Abstract

Induction of antibody-mediated immunity against hematologic malignancies requires CD4+ T-cell help, but weak tumor antigens generally fail to induce adequate T-cell responses, or to overcome tolerance. Conjugate vaccines can harness alternative help to activate responses, but memory B cells may then be exposed to leaking tumor-derived antigen without CD4+ T-cell support. We showed previously using lymphoma-derived idiotypic antigen that exposure to “helpless” antigen silences the majority of memory IgG+ B cells. Transfer experiments now indicate that silencing is permanent. In marked contrast to IgG, most coexisting IgM+ memory B cells exposed to “helpless” antigen survive. Confirmation in a hapten (NP) model allowed measurement of affinity, revealing this, rather than isotype, as the determinant of survival. IgM+ B cells had Ig variable region gene usage similar to IgG but with fewer somatic mutations. Survival of memory B cells appears variably controlled by affinity for antigen, allowing a minority of low affinity IgG+, but most IgM+, memory B cells to escape deletion in the absence of T-cell help. The latter remain, but the majority fail to undergo isotype switch. These findings could apply to other tumor antigens and are relevant for vaccination strategies aimed to induce long-term antibody.

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Published date: 21 July 2011
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 339298
URI: http://eprints.soton.ac.uk/id/eprint/339298
ISSN: 0006-4971
PURE UUID: 505ca622-542d-4393-a6e8-dffec777a86b

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Date deposited: 28 May 2012 14:01
Last modified: 18 Jul 2017 05:53

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Contributors

Author: Michael Shipton
Author: Amy Suchacki
Author: Gavin Babbage

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