A splenic IgM memory subset with antibacterial specificities is sustained from persistent mucosal responses

Simon Le Gallou, Zhicheng Zhou, Lan-Huong Thai, Remi Fritzen, Alba Verge de Los Aires, Jérôme Mégret, Philipp Yu, Daisuke Kitamura, Emmanuelle Bille, Fabiola Tros, Xavier Nassif, Alain Charbit, Sandra Weller, Jean-Claude Weill, Claude-Agnès Reynaud

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

To what extent immune responses against the gut flora are compartmentalized within mucosal tissues in homeostatic conditions remains a much-debated issue. We describe here, based on an inducible AID fate-mapping mouse model, that systemic memory B cell subsets, including mainly IgM+ B cells in spleen, together with IgA+ plasma cells in spleen and bone marrow, are generated in mice in the absence of deliberate immunization. While the IgA component appears dependent on the gut flora, IgM memory B cells are still generated in germ-free mice, albeit to a reduced extent. Clonal relationships and renewal kinetics after anti-CD20 treatment reveal that this long-lasting splenic population is mainly sustained by output of B cell clones persisting in mucosal germinal centers. IgM-secreting hybridomas established from splenic IgM memory B cells showed reactivity against various bacterial isolates and endogenous retroviruses. Ongoing activation of B cells in gut-associated lymphoid tissues thus generates a diversified systemic compartment showing long-lasting clonal persistence and protective capacity against systemic bacterial infections.

Original languageEnglish
Pages (from-to)2035-2053
Number of pages19
JournalJournal of Experimental Medicine
Volume215
Issue number8
Early online date29 Jun 2018
DOIs
Publication statusPublished - Aug 2018

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