B-cell intrinsic regulation of antibody mediated immunity by histone H2A deubiquitinase BAP1
IntroductionBAP1 is a deubiquitinase (DUB) of the Ubiquitin C-terminal Hydrolase (UCH) family that regulates gene expression and other cellular processes, through its direct catalytic activity on the repressive epigenetic mark histone H2AK119ub, as well as on several other substrates. BAP1 is also a...
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1353138/full |
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| author | Yue Liang Yue Liang HanChen Wang HanChen Wang HanChen Wang HanChen Wang Noé Seija Noé Seija Yun Hsiao Lin Yun Hsiao Lin Lin Tze Tung Lin Tze Tung Lin Tze Tung Lin Tze Tung Javier M. Di Noia Javier M. Di Noia Javier M. Di Noia Javier M. Di Noia David Langlais David Langlais David Langlais David Langlais Anastasia Nijnik Anastasia Nijnik |
| author_facet | Yue Liang Yue Liang HanChen Wang HanChen Wang HanChen Wang HanChen Wang Noé Seija Noé Seija Yun Hsiao Lin Yun Hsiao Lin Lin Tze Tung Lin Tze Tung Lin Tze Tung Lin Tze Tung Javier M. Di Noia Javier M. Di Noia Javier M. Di Noia Javier M. Di Noia David Langlais David Langlais David Langlais David Langlais Anastasia Nijnik Anastasia Nijnik |
| author_sort | Yue Liang |
| collection | DOAJ |
| description | IntroductionBAP1 is a deubiquitinase (DUB) of the Ubiquitin C-terminal Hydrolase (UCH) family that regulates gene expression and other cellular processes, through its direct catalytic activity on the repressive epigenetic mark histone H2AK119ub, as well as on several other substrates. BAP1 is also a highly important tumor suppressor, expressed and functional across many cell types and tissues. In recent work, we demonstrated a cell intrinsic role of BAP1 in the B cell lineage development in murine bone marrow, however the role of BAP1 in the regulation of B cell mediated humoral immune response has not been previously explored. Methods and resultsIn the current study, we demonstrate that a B-cell intrinsic loss of BAP1 in activated B cells in the Bap1fl/flCγ1-cre murine model results in a severe defect in antibody production, with altered dynamics of germinal centre B cell, memory B cell, and plasma cell numbers. At the cellular and molecular level, BAP1 was dispensable for B cell immunoglobulin class switching but resulted in an impaired proliferation of activated B cells, with genome-wide dysregulation in histone H2AK119ub levels and gene expression. Conclusion and discussionIn summary, our study establishes the B-cell intrinsic role of BAP1 in antibody mediated immune response and indicates its central role in the regulation of the genome-wide landscapes of histone H2AK119ub and downstream transcriptional programs of B cell activation and humoral immunity. |
| first_indexed | 2024-04-25T01:00:15Z |
| format | Article |
| id | doaj.art-2d7114a19c9f4754966093185d4ffaf5 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-25T01:00:15Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-2d7114a19c9f4754966093185d4ffaf52024-03-11T04:42:07ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-03-011510.3389/fimmu.2024.13531381353138B-cell intrinsic regulation of antibody mediated immunity by histone H2A deubiquitinase BAP1Yue Liang0Yue Liang1HanChen Wang2HanChen Wang3HanChen Wang4HanChen Wang5Noé Seija6Noé Seija7Yun Hsiao Lin8Yun Hsiao Lin9Lin Tze Tung10Lin Tze Tung11Lin Tze Tung12Lin Tze Tung13Javier M. Di Noia14Javier M. Di Noia15Javier M. Di Noia16Javier M. Di Noia17David Langlais18David Langlais19David Langlais20David Langlais21Anastasia Nijnik22Anastasia Nijnik23Department of Physiology, McGill University, Montreal, QC, CanadaMcGill University Research Centre on Complex Traits, McGill University, Montreal, QC, CanadaDepartment of Physiology, McGill University, Montreal, QC, CanadaMcGill University Research Centre on Complex Traits, McGill University, Montreal, QC, CanadaMcGill Genome Centre, Montreal, QC, CanadaDepartment of Human Genetics, McGill University, Montreal, QC, CanadaInstitut de Recherches Cliniques de Montréal, Montreal, QC, CanadaMolecular Biology Programs, Université de Montréal, Montreal, QC, CanadaDepartment of Physiology, McGill University, Montreal, QC, CanadaMcGill University Research Centre on Complex Traits, McGill University, Montreal, QC, CanadaDepartment of Physiology, McGill University, Montreal, QC, CanadaMcGill University Research Centre on Complex Traits, McGill University, Montreal, QC, CanadaMcGill Genome Centre, Montreal, QC, CanadaDepartment of Human Genetics, McGill University, Montreal, QC, CanadaInstitut de Recherches Cliniques de Montréal, Montreal, QC, CanadaMolecular Biology Programs, Université de Montréal, Montreal, QC, CanadaDepartment of Medicine, Université de Montréal, Montreal, QC, CanadaDepartment of Microbiology and Immunology, McGill University, Montreal, QC, CanadaMcGill University Research Centre on Complex Traits, McGill University, Montreal, QC, CanadaMcGill Genome Centre, Montreal, QC, CanadaDepartment of Human Genetics, McGill University, Montreal, QC, CanadaDepartment of Microbiology and Immunology, McGill University, Montreal, QC, CanadaDepartment of Physiology, McGill University, Montreal, QC, CanadaMcGill University Research Centre on Complex Traits, McGill University, Montreal, QC, CanadaIntroductionBAP1 is a deubiquitinase (DUB) of the Ubiquitin C-terminal Hydrolase (UCH) family that regulates gene expression and other cellular processes, through its direct catalytic activity on the repressive epigenetic mark histone H2AK119ub, as well as on several other substrates. BAP1 is also a highly important tumor suppressor, expressed and functional across many cell types and tissues. In recent work, we demonstrated a cell intrinsic role of BAP1 in the B cell lineage development in murine bone marrow, however the role of BAP1 in the regulation of B cell mediated humoral immune response has not been previously explored. Methods and resultsIn the current study, we demonstrate that a B-cell intrinsic loss of BAP1 in activated B cells in the Bap1fl/flCγ1-cre murine model results in a severe defect in antibody production, with altered dynamics of germinal centre B cell, memory B cell, and plasma cell numbers. At the cellular and molecular level, BAP1 was dispensable for B cell immunoglobulin class switching but resulted in an impaired proliferation of activated B cells, with genome-wide dysregulation in histone H2AK119ub levels and gene expression. Conclusion and discussionIn summary, our study establishes the B-cell intrinsic role of BAP1 in antibody mediated immune response and indicates its central role in the regulation of the genome-wide landscapes of histone H2AK119ub and downstream transcriptional programs of B cell activation and humoral immunity.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1353138/fullB cellhumoral immune responseepigenetic regulation and gene expressionmouse modelgerminal center (GC) B cellsclass switch recombination |
| spellingShingle | Yue Liang Yue Liang HanChen Wang HanChen Wang HanChen Wang HanChen Wang Noé Seija Noé Seija Yun Hsiao Lin Yun Hsiao Lin Lin Tze Tung Lin Tze Tung Lin Tze Tung Lin Tze Tung Javier M. Di Noia Javier M. Di Noia Javier M. Di Noia Javier M. Di Noia David Langlais David Langlais David Langlais David Langlais Anastasia Nijnik Anastasia Nijnik B-cell intrinsic regulation of antibody mediated immunity by histone H2A deubiquitinase BAP1 Frontiers in Immunology B cell humoral immune response epigenetic regulation and gene expression mouse model germinal center (GC) B cells class switch recombination |
| title | B-cell intrinsic regulation of antibody mediated immunity by histone H2A deubiquitinase BAP1 |
| title_full | B-cell intrinsic regulation of antibody mediated immunity by histone H2A deubiquitinase BAP1 |
| title_fullStr | B-cell intrinsic regulation of antibody mediated immunity by histone H2A deubiquitinase BAP1 |
| title_full_unstemmed | B-cell intrinsic regulation of antibody mediated immunity by histone H2A deubiquitinase BAP1 |
| title_short | B-cell intrinsic regulation of antibody mediated immunity by histone H2A deubiquitinase BAP1 |
| title_sort | b cell intrinsic regulation of antibody mediated immunity by histone h2a deubiquitinase bap1 |
| topic | B cell humoral immune response epigenetic regulation and gene expression mouse model germinal center (GC) B cells class switch recombination |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1353138/full |
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