A splenic IgM memory subset with antibacterial specificities is sustained from persistent mucosal responses
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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.
Le Gallou , S , Zhou , Z , Thai , L-H , Fritzen , R , de Los Aires , A V , Mégret , J , Yu , P , Kitamura , D , Bille , E , Tros , F , Nassif , X , Charbit , A , Weller , S , Weill , J-C & Reynaud , C-A 2018 , ' A splenic IgM memory subset with antibacterial specificities is sustained from persistent mucosal responses ' , Journal of Experimental Medicine , vol. 215 , no. 8 , pp. 2035-2053 . https://doi.org/10.1084/jem.20180977
Journal of Experimental Medicine
© 2018 Le Gallou et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4 .0/).
DescriptionThis work was supported by the Ligue contre le Cancer (“Equipe labellisée”), the Fondation Princesse Grace de Monaco, and the European Research Council Advanced grants “Memo-B” (to J.-C. Weill) and “B-response” (to C.-A. Reynaud). L.-H. Thai was supported by a Poste d'Accueil INS ERM.
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