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Limited clonal relatedness between gut IgA plasma cells and memory B cells after oral immunization

Bemark, Mats LU orcid ; Hazanov, Helena ; Strömberg, Anneli ; Komban, Rathan ; Holmqvist, Joel ; Köster, Sofia ; Mattsson, Johan ; Sikora, Per ; Mehr, Ramit and Lycke, Nils Y. (2016) In Nature Communications 7.
Abstract

Understanding how memory B cells are induced and relate to long-lived plasma cells is important for vaccine development. Immunity to oral vaccines has been considered short-lived because of a poor ability to develop IgA B-cell memory. Here we demonstrate that long-lived mucosal IgA memory is readily achieved by oral but not systemic immunization in mouse models with NP hapten conjugated with cholera toxin and transfer of B1-8high /GFP+ NP-specific B cells. Unexpectedly, memory B cells are poorly related to long-lived plasma cells and less affinity-matured. They are α4β7-integrin+ CD73+ PD-L2+ CD80+ and at systemic sites mostly IgM+, while 80% are... (More)

Understanding how memory B cells are induced and relate to long-lived plasma cells is important for vaccine development. Immunity to oral vaccines has been considered short-lived because of a poor ability to develop IgA B-cell memory. Here we demonstrate that long-lived mucosal IgA memory is readily achieved by oral but not systemic immunization in mouse models with NP hapten conjugated with cholera toxin and transfer of B1-8high /GFP+ NP-specific B cells. Unexpectedly, memory B cells are poorly related to long-lived plasma cells and less affinity-matured. They are α4β7-integrin+ CD73+ PD-L2+ CD80+ and at systemic sites mostly IgM+, while 80% are IgA+ in Peyer's patches. On reactivation, most memory B cells in Peyer's patches are GL7+, but expand in germinal centres and acquire higher affinity and more mutations, demonstrating strong clonal selection. CCR9 expression is found only in Peyer's patches and appears critical for gut homing. Thus, gut mucosal memory possesses unique features not seen after systemic immunization.

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author
; ; ; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
7
article number
12698
publisher
Nature Publishing Group
external identifiers
  • pmid:27596266
  • scopus:84986568270
ISSN
2041-1723
DOI
10.1038/ncomms12698
language
English
LU publication?
no
additional info
Publisher Copyright: © 2016 The Author(s).
id
46385a0c-70fe-4766-b245-a9fb21187dab
date added to LUP
2023-11-28 10:26:09
date last changed
2024-11-08 10:33:18
@article{46385a0c-70fe-4766-b245-a9fb21187dab,
  abstract     = {{<p>Understanding how memory B cells are induced and relate to long-lived plasma cells is important for vaccine development. Immunity to oral vaccines has been considered short-lived because of a poor ability to develop IgA B-cell memory. Here we demonstrate that long-lived mucosal IgA memory is readily achieved by oral but not systemic immunization in mouse models with NP hapten conjugated with cholera toxin and transfer of B1-8<sup>high</sup> /GFP<sup>+</sup> NP-specific B cells. Unexpectedly, memory B cells are poorly related to long-lived plasma cells and less affinity-matured. They are α4β7-integrin<sup>+</sup> CD73<sup>+</sup> PD-L2<sup>+</sup> CD80<sup>+</sup> and at systemic sites mostly IgM<sup>+</sup>, while 80% are IgA<sup>+</sup> in Peyer's patches. On reactivation, most memory B cells in Peyer's patches are GL7<sup>+</sup>, but expand in germinal centres and acquire higher affinity and more mutations, demonstrating strong clonal selection. CCR9 expression is found only in Peyer's patches and appears critical for gut homing. Thus, gut mucosal memory possesses unique features not seen after systemic immunization.</p>}},
  author       = {{Bemark, Mats and Hazanov, Helena and Strömberg, Anneli and Komban, Rathan and Holmqvist, Joel and Köster, Sofia and Mattsson, Johan and Sikora, Per and Mehr, Ramit and Lycke, Nils Y.}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  month        = {{09}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Limited clonal relatedness between gut IgA plasma cells and memory B cells after oral immunization}},
  url          = {{http://dx.doi.org/10.1038/ncomms12698}},
  doi          = {{10.1038/ncomms12698}},
  volume       = {{7}},
  year         = {{2016}},
}