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

被引:152
作者
Magri, Giuliana [1 ]
Comerma, Laura [1 ]
Pybus, Marc [1 ]
Sintes, Jordi [1 ]
Llige, David [1 ]
Segura-Garzon, Daniel [1 ]
Bascones, Sabrina [1 ]
Yeste, Ada [1 ]
Grasset, Emilie K. [2 ,3 ]
Gutzeit, Cindy [2 ]
Uzzan, Mathieu [2 ]
Ramanujam, Meera [4 ]
van Zelm, Menno C. [5 ,6 ]
Albero-Gonzalez, Raquel [7 ]
Vazquez, Ivonne [7 ]
Iglesias, Mar [7 ,8 ]
Serrano, Sergi [7 ,8 ]
Marquez, Lucia [9 ]
Mercade, Elena [10 ]
Mehandru, Saurabh [2 ]
Cerutti, Andrea [1 ,2 ,11 ]
机构
[1] Inst Hosp Mar Invest Med IMIM, Program Inflammatory & Cardiovasc Disorders, Barcelona 08003, Spain
[2] Icahn Sch Med Mt Sinai, Inst Immunol, Dept Med, New York, NY 10029 USA
[3] Karolinska Inst, Karolinska Univ Hosp, Ctr Mol Med, Dept Med, S-17176 Stockholm, Sweden
[4] Boehringer Ingelheim Pharmaceut, Immunol & Resp Dis Res, Ridgefield, CT 06877 USA
[5] Monash Univ, Dept Immunol & Pathol, Melbourne, Vic 3004, Australia
[6] Alfred Hosp, Melbourne, Vic 3004, Australia
[7] Hosp Mar, Dept Pathol, Barcelona 08003, Spain
[8] Univ Autonoma Barcelona, Barcelona 08003, Spain
[9] Hosp Mar, Dept Gastroenterol, Barcelona 08003, Spain
[10] Univ Barcelona, Dept Biol Hlth & Environm, E-08028 Barcelona, Spain
[11] Catalan Inst Res & Adv Studies ICREA, Barcelona 08003, Spain
关键词
LYMPHOID-TISSUE; SEQUENCING DATA; MICROBIOTA; GENERATION; RESPONSES; DIVERSIFICATION; REPERTOIRES; POPULATION; EXPRESSION; CAPACITIES;
D O I
10.1016/j.immuni.2017.06.013
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:118 / +
页数:25
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