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

Giuliana Magri, Laura Comerma, Marc Pybus, Jordi Sintes, David Lligé, Daniel Segura-Garzón, Sabrina Bascones, Ada Yeste, Emilie K. Grasset, Cindy Gutzeit, Mathieu Uzzan, Meera Ramanujam, Menno C. van Zelm, Raquel Albero-González, Ivonne Vazquez, Mar Iglesias, Sergi Serrano, Lucía Márquez, Elena Mercade, Saurabh MehandruAndrea Cerutti

Research output: Contribution to journalArticleResearchpeer-review

43 Citations (Scopus)

Abstract

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. Magri et al. found that the human gut includes a large memory IgM+ B cell repertoire clonally related to plasma cells mounting SIgM responses against mucus-embedded commensals co-targeted by SIgA. Dually coated bacteria are detected in humans but not mice and show increased diversity and richness compared to SIgA-only-coated or uncoated bacteria.

Original languageEnglish
Pages (from-to)118-134
Number of pages17
JournalImmunity
Volume47
Issue number1
DOIs
Publication statusPublished - 18 Jul 2017

Keywords

  • Gut
  • Human
  • IgA
  • IgM
  • Memory B cells
  • Microbiota
  • Mucosa
  • Plasma cells
  • Repertoire

Cite this

Magri, G., Comerma, L., Pybus, M., Sintes, J., Lligé, D., Segura-Garzón, D., Bascones, S., Yeste, A., Grasset, E. K., Gutzeit, C., Uzzan, M., Ramanujam, M., van Zelm, M. C., Albero-González, R., Vazquez, I., Iglesias, M., Serrano, S., Márquez, L., Mercade, E., ... Cerutti, A. (2017). Human Secretory IgM Emerges from Plasma Cells Clonally Related to Gut Memory B Cells and Targets Highly Diverse Commensals. Immunity, 47(1), 118-134. https://doi.org/10.1016/j.immuni.2017.06.013