AUTHOR=Lin Yun Hsiao , Liang Yue , Wang HanChen , Tung Lin Tze , Förster Michael , Subramani Poorani Ganesh , Di Noia Javier M. , Clare Simon , Langlais David , Nijnik Anastasia 

TITLE=Regulation of B Lymphocyte Development by Histone H2A Deubiquitinase BAP1

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.626418

DOI=10.3389/fimmu.2021.626418

ISSN=1664-3224

ABSTRACT=<p>BAP1 is a deubiquitinase (DUB) of the Ubiquitin C-terminal Hydrolase (UCH) family that regulates gene expression and other cellular processes, <italic>via</italic> deubiquitination of histone H2AK119ub and other substrates. BAP1 is an important tumor suppressor in human, expressed and functional across many cell-types and tissues, including those of the immune system. B lymphocytes are the mediators of humoral immune response, however the role of BAP1 in B cell development and physiology remains poorly understood. Here we characterize a mouse line with a selective deletion of BAP1 within the B cell lineage (<italic>Bap1</italic><sup>fl/fl</sup> mb1-<italic>Cre</italic>) and establish a cell intrinsic role of BAP1 in the regulation of B cell development. We demonstrate a depletion of large pre-B cells, transitional B cells, and mature B cells in <italic>Bap1</italic><sup>fl/fl</sup> mb1-<italic>Cre</italic> mice. We characterize broad transcriptional changes in BAP1-deficient pre-B cells, map BAP1 binding across the genome, and analyze the effects of BAP1-loss on histone H2AK119ub levels and distribution. Overall, our work establishes a cell intrinsic role of BAP1 in B lymphocyte development, and suggests its contribution to the regulation of the transcriptional programs of cell cycle progression, <italic>via</italic> the deubiquitination of histone H2AK119ub.</p>