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

Magri, Giuliana, 1978-; Pybus Oliveras, Marc, 1985-; Sintes, Jordi; Lligé, David; Segura-Garzón, Daniel; Bascones Gleave, Sabrina, 1985-; Yeste, Ada; Grasset, Emilie K.; Gutzeit, Cindy; Uzzan, Mathieu; Ramanujam, Meera; van Zelm, Menno C.; Albero-González, Raquel; Vazquez de las Heras, Ivonne; Iglesias, Mar; Serrano Figueras, Sergi; Márquez, Lucía; Mercade, Elena; Mehandru, Saurabh; Cerutti, Andrea, 1965-

doi:http://dx.doi.org/10.1016/j.immuni.2017.06.013

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

Citation

Magri G, Comerma L, Pybus M, Sintes J, Lligé D, Segura-Garzón D. et al. 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

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.