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

J Exp Med. 2018 Aug 6;215(8):2035-2053. doi: 10.1084/jem.20180977. Epub 2018 Jun 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / immunology
  • Animals
  • Anti-Bacterial Agents / immunology*
  • Antigens, CD / metabolism
  • B-Lymphocytes / immunology
  • Bacterial Proteins / metabolism
  • Bone Marrow / metabolism
  • Cytidine Deaminase / metabolism
  • Gastrointestinal Microbiome
  • Germ-Free Life
  • Germinal Center / cytology
  • Immunity, Mucosal*
  • Immunization
  • Immunoglobulin A / metabolism
  • Immunoglobulin M / metabolism*
  • Immunologic Memory*
  • Kinetics
  • Luminescent Proteins / metabolism
  • Mice
  • Mutation / genetics
  • Plasma Cells / cytology
  • Signal Transduction
  • Spleen / immunology*
  • T-Lymphocytes / metabolism
  • Toll-Like Receptors / metabolism


  • Anti-Bacterial Agents
  • Antigens, CD
  • Bacterial Proteins
  • Immunoglobulin A
  • Immunoglobulin M
  • Luminescent Proteins
  • Toll-Like Receptors
  • secretory IgM
  • yellow fluorescent protein, Bacteria
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase

Associated data

  • GENBANK/AC158651