B-cell intrinsic regulation of antibody mediated immunity by histone H2A deubiquitinase BAP1

• DOI: 10.3389/fimmu.2024.1353138
• Publication Date: 2024-03-11T04:41:58Z
• Authors: Yue Liang; HanChen Wang; Noé Seija; Yun Hsiao Lin; Lin Tze Tung; Javier M. Di Noia; David Langlais; Anastasia Nijnik
• Keywords: Deubiquitinating enzyme; BAP1

Introduction BAP1 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 repressive epigenetic mark histone H2AK119ub, as well several substrates. also highly important tumor suppressor, expressed functional across many cell types tissues. In recent work, we demonstrated intrinsic role in B lineage development murine bone marrow, however regulation mediated humoral immune response has not been previously explored. Methods results current study, demonstrate B-cell loss activated cells Bap1 fl/fl Cγ1 -cre model severe defect antibody production, with altered dynamics germinal centre cell, memory plasma numbers. At molecular level, was dispensable for immunoglobulin class switching but resulted an impaired proliferation cells, genome-wide dysregulation H2AK119ub levels expression. Conclusion discussion summary, our study establishes indicates central landscapes downstream transcriptional programs activation immunity.