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...
Saved in:
Main Authors: | , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wiley
2022-01-01
|
Series: | Journal of Immunology Research |
Online Access: | http://dx.doi.org/10.1155/2022/3974141 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
_version_ | 1832562562477064192 |
---|---|
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. |
format | Article |
id | doaj-art-c6303fb4b2b74513b2c0878cc2cbb81e |
institution | Kabale University |
issn | 2314-7156 |
language | English |
publishDate | 2022-01-01 |
publisher | Wiley |
record_format | Article |
series | Journal of Immunology Research |
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 |
work_keys_str_mv | AT masatotsuda cecalpatchesgenerateabundantigg2bbearingbcellsthatarereactivetocommensalmicrobiota AT hirakuokada cecalpatchesgenerateabundantigg2bbearingbcellsthatarereactivetocommensalmicrobiota AT natsukikojima cecalpatchesgenerateabundantigg2bbearingbcellsthatarereactivetocommensalmicrobiota AT fumiyaishihama cecalpatchesgenerateabundantigg2bbearingbcellsthatarereactivetocommensalmicrobiota AT yuheimuraki cecalpatchesgenerateabundantigg2bbearingbcellsthatarereactivetocommensalmicrobiota AT toshikioguma cecalpatchesgenerateabundantigg2bbearingbcellsthatarereactivetocommensalmicrobiota AT nanakohattori cecalpatchesgenerateabundantigg2bbearingbcellsthatarereactivetocommensalmicrobiota AT takumimizoguchi cecalpatchesgenerateabundantigg2bbearingbcellsthatarereactivetocommensalmicrobiota AT kiyoakimori cecalpatchesgenerateabundantigg2bbearingbcellsthatarereactivetocommensalmicrobiota AT satoshihachimura cecalpatchesgenerateabundantigg2bbearingbcellsthatarereactivetocommensalmicrobiota AT yoshimasatakahashi cecalpatchesgenerateabundantigg2bbearingbcellsthatarereactivetocommensalmicrobiota AT kyokotakahashi cecalpatchesgenerateabundantigg2bbearingbcellsthatarereactivetocommensalmicrobiota AT shuichikaminogawa cecalpatchesgenerateabundantigg2bbearingbcellsthatarereactivetocommensalmicrobiota AT akirahosono cecalpatchesgenerateabundantigg2bbearingbcellsthatarereactivetocommensalmicrobiota |