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Microbe-dependent CD11b+ IgA+ plasma cells in early-phase robust intestinal IgA responses in mice

Nature Communications 4, 1772 doi:10.1038/ncomms2718
Jun Kunisawa, Masashi Gohda, Eri Hashimoto, Izumi Ishikawa, Morio Higuchi, Yuji Suzuki, Yoshiyuki Goto, Casandra Panea, Ivaylo I. Ivanov, Risa Sumiya, Lamichhane Aayam, Taichi Wake, So Tajiri, Yosuke Kurashima, Shiori Shikata, Shizuo Akira, Kiyoshi Takeda & Hiroshi Kiyono
Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Department of Medical Genome Science, Graduate School of Frontier Science, The University of Tokyo, Chiba 277-8562, Japan
International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Laboratory of Vaccine Materials, National Institute of Biomedical Innovation, Osaka 567-0085, Japan
Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo 102-0075, Japan
Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan
Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York 10032, USA
Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan
Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan

Intestinal plasma cells predominantly produce immunoglobulin (Ig) A, however, their functional diversity remains poorly characterized. Here we show that murine intestinal IgA plasma cells can be newly classified into two populations on the basis of CD11b expression, which cannot be discriminated by currently known criteria such as general plasma cell markers, B cell origin and T cell dependence. CD11b+ IgA+ plasma cells require the lymphoid structure of Peyer's patches, produce more IgA than CD11b− IgA+ plasma cells, proliferate vigorously, and require microbial stimulation and IL-10 for their development and maintenance. These features allow CD11b+ IgA+ plasma cells to mediate early-phase antigen-specific intestinal IgA responses induced by oral immunization with protein antigen. These findings reveal the functional diversity of IgA+ plasma cells in the murine intestine.