Epigenetic Regulation of Antibody Responses by the Histone H2A Deubiquitinase MYSM1

Scientific Reports
Xiao-Xia JiangSi-Yi Chen

Abstract

B cell-mediated antibody response plays critical roles in protective immunity, as well as in the pathogenesis of allergic and autoimmune diseases. Epigenetic histone and DNA modifications regulate gene transcription and immunity; however, so far, little is known about the role of epigenetic regulation in antibody responses. In this study, we found that mice deficient in the histone H2A deubiquitinase MYSM1, despite their severe defect in B cell development, exhibit an enhanced antibody response against both T cell-dependent and independent antigens. We revealed that MYSM1 intrinsically represses plasma cell differentiation and antibody production. Mechanistic studies demonstrated that MYSM1 is a transcriptional activator of Pax5, the repressors of plasma cell differentiation, by facilitating key transcriptional factor recruitment and coordinating histone modifications at the Pax5 loci. Hence, this study uncovers a critical role for MYSM1 in epigenetically repressing plasma cell differentiation and antibody production, in addition to its opposing, active role in B cell development. Importantly, this study further provides a new target and strategy to modulate antibody production and responses with profound therapeutic implications.

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Citations

Jan 23, 2016·Current Opinion in Immunology·Lynn M Corcoran, David M Tarlinton
Jan 25, 2017·The Journal of Allergy and Clinical Immunology·Ehsan BahramiChristoph Klein
Nov 6, 2018·Molecular Biology Reports·Xin ZhaoXiao-Xia Jiang
Jan 1, 2017·The Journal of Biological Chemistry·Claudia LentucciValentina Perissi
Apr 30, 2020·International Journal of Molecular Sciences·Amanda FioreAnastasia Nijnik
Dec 7, 2018·Allergologia et immunopathologia·S Afshar-GhasemlouA Rezaei
Aug 16, 2021·The Journal of Biological Chemistry·Nathan A Snyder, Gustavo M Silva

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Methods Mentioned

BETA
deubiquitination
flow cytometry
ELISA
ChIP
co-immunoprecipitation
membrane filtration
PCR
Immunoprecipitation

Software Mentioned

TreeStar
FlowJo

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