TY - JOUR
T1 - A splenic IgM memory subset with antibacterial specificities is sustained from persistent mucosal responses
AU - Le Gallou, Simon
AU - Zhou, Zhicheng
AU - Thai, Lan-Huong
AU - Fritzen, Remi
AU - de Los Aires, Alba Verge
AU - Mégret, Jérôme
AU - Yu, Philipp
AU - Kitamura, Daisuke
AU - Bille, Emmanuelle
AU - Tros, Fabiola
AU - Nassif, Xavier
AU - Charbit, Alain
AU - Weller, Sandra
AU - Weill, Jean-Claude
AU - Reynaud, Claude-Agnès
N1 - This 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.
PY - 2018/8
Y1 - 2018/8
N2 - 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.
AB - 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.
U2 - 10.1084/jem.20180977
DO - 10.1084/jem.20180977
M3 - Article
C2 - 29959173
SN - 0022-1007
VL - 215
SP - 2035
EP - 2053
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 8
ER -