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

Mats Bemark (), Helena Hazanov, Anneli Strömberg, Rathan Komban, Joel Holmqvist, Sofia Köster, Johan Mattsson, Per Sikora, Ramit Mehr and Nils Y. Lycke ()
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Mats Bemark: Institute of Biomedicine, University of Gothenburg
Helena Hazanov: Computational Immunology Lab, The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University
Anneli Strömberg: Institute of Biomedicine, University of Gothenburg
Rathan Komban: Institute of Biomedicine, University of Gothenburg
Joel Holmqvist: Institute of Biomedicine, University of Gothenburg
Sofia Köster: Institute of Biomedicine, University of Gothenburg
Johan Mattsson: Institute of Biomedicine, University of Gothenburg
Per Sikora: Sahlgrenska University Hospital
Ramit Mehr: Computational Immunology Lab, The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University
Nils Y. Lycke: Institute of Biomedicine, University of Gothenburg

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: 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 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.

Date: 2016
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DOI: 10.1038/ncomms12698

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