Human Secretory IgM Emerges from Plasma Cells Clonally Related to Gut Memory B Cells and Targets Highly Diverse Commensals

Immunity. 2017 Jul 18;47(1):118-134.e8. doi: 10.1016/j.immuni.2017.06.013. Epub 2017 Jul 11.


Secretory immunoglobulin A (SIgA) enhances host-microbiota symbiosis, whereas SIgM remains poorly understood. We found that gut IgM+ plasma cells (PCs) were more abundant in humans than mice and clonally related to a large repertoire of memory IgM+ B cells disseminated throughout the intestine but rare in systemic lymphoid organs. In addition to sharing a gut-specific gene signature with memory IgA+ B cells, memory IgM+ B cells were related to some IgA+ clonotypes and switched to IgA in response to T cell-independent or T cell-dependent signals. These signals induced abundant IgM which, together with SIgM from clonally affiliated PCs, recognized mucus-embedded commensals. Bacteria recognized by human SIgM were dually coated by SIgA and showed increased richness and diversity compared to IgA-only-coated or uncoated bacteria. Thus, SIgM may emerge from pre-existing memory rather than newly activated naive IgM+ B cells and could help SIgA to anchor highly diverse commensal communities to mucus.

Keywords: IgA; IgM; gut; human; memory B cells; microbiota; mucosa; plasma cells; repertoire.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiodysplasia / immunology*
  • Animals
  • B-Lymphocytes / immunology*
  • Clone Cells
  • Colonic Neoplasms / immunology*
  • Colonic Polyps / immunology*
  • Female
  • Gastrointestinal Microbiome / immunology
  • Humans
  • Immunity, Mucosal
  • Immunoglobulin A / metabolism
  • Immunoglobulin Class Switching
  • Immunoglobulin M / metabolism*
  • Immunologic Memory
  • Intestines / immunology*
  • Intestines / microbiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Plasma Cells / immunology*
  • Symbiosis


  • Immunoglobulin A
  • Immunoglobulin M