Cecal Patches Generate Abundant IgG2b-Bearing B Cells That Are Reactive to Commensal Microbiota

Gut-associated lymphoid tissue (GALT), such as Peyer’s patches (PPs), are key inductive sites that generate IgA+ B cells, mainly through germinal center (GC) responses. The generation of IgA+ B cells is promoted by the presence of gut microbiota and dietary antigens. However, the function of GALT in...

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Main Authors: Masato Tsuda, Hiraku Okada, Natsuki Kojima, Fumiya Ishihama, Yuhei Muraki, Toshiki Oguma, Nanako Hattori, Takumi Mizoguchi, Kiyoaki Mori, Satoshi Hachimura, Yoshimasa Takahashi, Kyoko Takahashi, Shuichi Kaminogawa, Akira Hosono
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2022/3974141
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author Masato Tsuda
Hiraku Okada
Natsuki Kojima
Fumiya Ishihama
Yuhei Muraki
Toshiki Oguma
Nanako Hattori
Takumi Mizoguchi
Kiyoaki Mori
Satoshi Hachimura
Yoshimasa Takahashi
Kyoko Takahashi
Shuichi Kaminogawa
Akira Hosono
author_facet Masato Tsuda
Hiraku Okada
Natsuki Kojima
Fumiya Ishihama
Yuhei Muraki
Toshiki Oguma
Nanako Hattori
Takumi Mizoguchi
Kiyoaki Mori
Satoshi Hachimura
Yoshimasa Takahashi
Kyoko Takahashi
Shuichi Kaminogawa
Akira Hosono
author_sort Masato Tsuda
collection DOAJ
description Gut-associated lymphoid tissue (GALT), such as Peyer’s patches (PPs), are key inductive sites that generate IgA+ B cells, mainly through germinal center (GC) responses. The generation of IgA+ B cells is promoted by the presence of gut microbiota and dietary antigens. However, the function of GALT in the large intestine, such as cecal patches (CePs) and colonic patches (CoPs), and their regulatory mechanisms remain largely unknown. In this study, we demonstrate that the CePs possess more IgG2b+ B cells and have fewer IgA+ B cells than those in PPs from BALB/c mice with normal gut microbiota. Gene expression analysis of postswitched transcripts supported the differential expression of dominant antibody isotypes in B cells in GALT. Germ-free (GF) mice showed diminished GC B cells and had few IgA+ or IgG2b+ switched B cells in both the small and large intestinal GALT. In contrast, myeloid differentiation factor 88- (MyD88-) deficient mice exhibited decreased GC B cells and presented with reduced numbers of IgG2b+ B cells in CePs but not in PPs. Using ex vivo cell culture, we showed that CePs have a greater capacity to produce total and microbiota-reactive IgG2b, in addition to microbiota-reactive IgA, than the PPs. In line with the frequency of GC B cells and IgG2b+ B cells in CePs, there was a decrease in the levels of microbiota-reactive IgG2b and IgA in the serum of GF and MyD88-deficient mice. These data suggest that CePs have a different antibody production profile compared to PPs. Furthermore, the innate immune signals derived from gut microbiota are crucial for generating the IgG2b antibodies in CePs.
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spelling doaj-art-c6303fb4b2b74513b2c0878cc2cbb81e2025-02-03T01:22:27ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/3974141Cecal Patches Generate Abundant IgG2b-Bearing B Cells That Are Reactive to Commensal MicrobiotaMasato Tsuda0Hiraku Okada1Natsuki Kojima2Fumiya Ishihama3Yuhei Muraki4Toshiki Oguma5Nanako Hattori6Takumi Mizoguchi7Kiyoaki Mori8Satoshi Hachimura9Yoshimasa Takahashi10Kyoko Takahashi11Shuichi Kaminogawa12Akira Hosono13Department of Food Bioscience and BiotechnologyDepartment of Food Bioscience and BiotechnologyDepartment of Food Bioscience and BiotechnologyDepartment of Food Bioscience and BiotechnologyDepartment of Food Bioscience and BiotechnologyDepartment of Food Bioscience and BiotechnologyDepartment of Food Bioscience and BiotechnologyDepartment of Food Bioscience and BiotechnologyDepartment of Food Bioscience and BiotechnologyResearch Center for Food SafetyResearch Center for Drug and Vaccine DevelopmentDepartment of Food Bioscience and BiotechnologyDepartment of Food Bioscience and BiotechnologyDepartment of Food Bioscience and BiotechnologyGut-associated lymphoid tissue (GALT), such as Peyer’s patches (PPs), are key inductive sites that generate IgA+ B cells, mainly through germinal center (GC) responses. The generation of IgA+ B cells is promoted by the presence of gut microbiota and dietary antigens. However, the function of GALT in the large intestine, such as cecal patches (CePs) and colonic patches (CoPs), and their regulatory mechanisms remain largely unknown. In this study, we demonstrate that the CePs possess more IgG2b+ B cells and have fewer IgA+ B cells than those in PPs from BALB/c mice with normal gut microbiota. Gene expression analysis of postswitched transcripts supported the differential expression of dominant antibody isotypes in B cells in GALT. Germ-free (GF) mice showed diminished GC B cells and had few IgA+ or IgG2b+ switched B cells in both the small and large intestinal GALT. In contrast, myeloid differentiation factor 88- (MyD88-) deficient mice exhibited decreased GC B cells and presented with reduced numbers of IgG2b+ B cells in CePs but not in PPs. Using ex vivo cell culture, we showed that CePs have a greater capacity to produce total and microbiota-reactive IgG2b, in addition to microbiota-reactive IgA, than the PPs. In line with the frequency of GC B cells and IgG2b+ B cells in CePs, there was a decrease in the levels of microbiota-reactive IgG2b and IgA in the serum of GF and MyD88-deficient mice. These data suggest that CePs have a different antibody production profile compared to PPs. Furthermore, the innate immune signals derived from gut microbiota are crucial for generating the IgG2b antibodies in CePs.http://dx.doi.org/10.1155/2022/3974141
spellingShingle Masato Tsuda
Hiraku Okada
Natsuki Kojima
Fumiya Ishihama
Yuhei Muraki
Toshiki Oguma
Nanako Hattori
Takumi Mizoguchi
Kiyoaki Mori
Satoshi Hachimura
Yoshimasa Takahashi
Kyoko Takahashi
Shuichi Kaminogawa
Akira Hosono
Cecal Patches Generate Abundant IgG2b-Bearing B Cells That Are Reactive to Commensal Microbiota
Journal of Immunology Research
title Cecal Patches Generate Abundant IgG2b-Bearing B Cells That Are Reactive to Commensal Microbiota
title_full Cecal Patches Generate Abundant IgG2b-Bearing B Cells That Are Reactive to Commensal Microbiota
title_fullStr Cecal Patches Generate Abundant IgG2b-Bearing B Cells That Are Reactive to Commensal Microbiota
title_full_unstemmed Cecal Patches Generate Abundant IgG2b-Bearing B Cells That Are Reactive to Commensal Microbiota
title_short Cecal Patches Generate Abundant IgG2b-Bearing B Cells That Are Reactive to Commensal Microbiota
title_sort cecal patches generate abundant igg2b bearing b cells that are reactive to commensal microbiota
url http://dx.doi.org/10.1155/2022/3974141
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