H3K36 methyltransferase NSD1 is essential for normal B1 and B2 cell development and germinal center formation

B cells, which consist of two well-defined populations: B1 and B2 cells, which can produce antibodies that are essential for host protection against infections, through virus neutralization, opsonization and antibody-dependent cellular cytotoxicity. Epigenetic modifications, such as DNA methylation...

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Main Authors: Sulan Zhai, Min Cao, Han Zhou, Huamin Zhu, Tongchang Xu, Yuliang Wang, Xiaoming Wang, Zhenming Cai
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-11-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.959021/full
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author Sulan Zhai
Min Cao
Han Zhou
Han Zhou
Huamin Zhu
Tongchang Xu
Yuliang Wang
Xiaoming Wang
Xiaoming Wang
Xiaoming Wang
Zhenming Cai
author_facet Sulan Zhai
Min Cao
Han Zhou
Han Zhou
Huamin Zhu
Tongchang Xu
Yuliang Wang
Xiaoming Wang
Xiaoming Wang
Xiaoming Wang
Zhenming Cai
author_sort Sulan Zhai
collection DOAJ
description B cells, which consist of two well-defined populations: B1 and B2 cells, which can produce antibodies that are essential for host protection against infections, through virus neutralization, opsonization and antibody-dependent cellular cytotoxicity. Epigenetic modifications, such as DNA methylation and histone modification could regulate immune cell differentiation and functions. In this study, we found a significant reduction of GC response in the B cell specific knockout of H3K36 methyltransferase NSD1 (Mb1-Cre+ NSD1fl/fl, NSD1B KO) mice compared with the wildtype control (Mb1-Cre+ NSD1+/+, NSD1B WT). We also demonstrated reduced production of high-affinity antibody, but increased production of low-affinity antibody in the NSD1B KO mice. Further analysis revealed that loss of NSD1 promoted the development of B1 cells by increasing the expression of Rap1b and Arid3a. In conclusion, our data suggest that NSD1 plays an important role in regulation the development of B1 and B2 cells, and the process of germinal center formation and high-affinity antibody production.
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spelling doaj.art-caeba1ad6f62450190cca9466f411b5a2022-12-22T03:45:15ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.959021959021H3K36 methyltransferase NSD1 is essential for normal B1 and B2 cell development and germinal center formationSulan Zhai0Min Cao1Han Zhou2Han Zhou3Huamin Zhu4Tongchang Xu5Yuliang Wang6Xiaoming Wang7Xiaoming Wang8Xiaoming Wang9Zhenming Cai10Department of Immunology, Key Laboratory of Immune Microenvironment and Diseases, Nanjing Medical University, Nanjing, ChinaDepartment of Immunology, Key Laboratory of Immune Microenvironment and Diseases, Nanjing Medical University, Nanjing, ChinaDepartment of Immunology, Key Laboratory of Immune Microenvironment and Diseases, Nanjing Medical University, Nanjing, ChinaReproductive Medicine Centre, Changzhou No. 2 People’s Hospital, The Affiliated Hospital of Nanjing Medical University, Changzhou, ChinaDepartment of Immunology, Key Laboratory of Immune Microenvironment and Diseases, Nanjing Medical University, Nanjing, ChinaDepartment of Immunology, Key Laboratory of Immune Microenvironment and Diseases, Nanjing Medical University, Nanjing, ChinaDepartment of Immunology, Key Laboratory of Immune Microenvironment and Diseases, Nanjing Medical University, Nanjing, ChinaDepartment of Immunology, Key Laboratory of Immune Microenvironment and Diseases, Nanjing Medical University, Nanjing, ChinaState Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, ChinaNational Health Commission (NHC) Key Laboratory of Antibody Technique, Nanjing Medical University, Nanjing, ChinaDepartment of Immunology, Key Laboratory of Immune Microenvironment and Diseases, Nanjing Medical University, Nanjing, ChinaB cells, which consist of two well-defined populations: B1 and B2 cells, which can produce antibodies that are essential for host protection against infections, through virus neutralization, opsonization and antibody-dependent cellular cytotoxicity. Epigenetic modifications, such as DNA methylation and histone modification could regulate immune cell differentiation and functions. In this study, we found a significant reduction of GC response in the B cell specific knockout of H3K36 methyltransferase NSD1 (Mb1-Cre+ NSD1fl/fl, NSD1B KO) mice compared with the wildtype control (Mb1-Cre+ NSD1+/+, NSD1B WT). We also demonstrated reduced production of high-affinity antibody, but increased production of low-affinity antibody in the NSD1B KO mice. Further analysis revealed that loss of NSD1 promoted the development of B1 cells by increasing the expression of Rap1b and Arid3a. In conclusion, our data suggest that NSD1 plays an important role in regulation the development of B1 and B2 cells, and the process of germinal center formation and high-affinity antibody production.https://www.frontiersin.org/articles/10.3389/fimmu.2022.959021/fullNSD1B2 cellsgerminal centerantibodyB1 cells
spellingShingle Sulan Zhai
Min Cao
Han Zhou
Han Zhou
Huamin Zhu
Tongchang Xu
Yuliang Wang
Xiaoming Wang
Xiaoming Wang
Xiaoming Wang
Zhenming Cai
H3K36 methyltransferase NSD1 is essential for normal B1 and B2 cell development and germinal center formation
Frontiers in Immunology
NSD1
B2 cells
germinal center
antibody
B1 cells
title H3K36 methyltransferase NSD1 is essential for normal B1 and B2 cell development and germinal center formation
title_full H3K36 methyltransferase NSD1 is essential for normal B1 and B2 cell development and germinal center formation
title_fullStr H3K36 methyltransferase NSD1 is essential for normal B1 and B2 cell development and germinal center formation
title_full_unstemmed H3K36 methyltransferase NSD1 is essential for normal B1 and B2 cell development and germinal center formation
title_short H3K36 methyltransferase NSD1 is essential for normal B1 and B2 cell development and germinal center formation
title_sort h3k36 methyltransferase nsd1 is essential for normal b1 and b2 cell development and germinal center formation
topic NSD1
B2 cells
germinal center
antibody
B1 cells
url https://www.frontiersin.org/articles/10.3389/fimmu.2022.959021/full
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