AUTHOR=Singh Amit , Kaileh Mary , De Supriyo , Mazan-Mamczarz Krystyna , Bayarsaihan Dashzeveg , Sen Ranjan , Roy Ananda L. 

TITLE=Transcription factor TFII-I fine tunes innate properties of B lymphocytes

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1067459

DOI=10.3389/fimmu.2023.1067459

ISSN=1664-3224

ABSTRACT=<p>The ubiquitously expressed transcription factor TFII-I is a multifunctional protein with pleiotropic roles in gene regulation. TFII-I associated polymorphisms are implicated in Sjögren’s syndrome and Lupus in humans and, germline deletion of the <italic>Gtf2i</italic> gene in mice leads to embryonic lethality. Here we report a unique role for TFII-I in homeostasis of innate properties of B lymphocytes. Loss of <italic>Gtf2i</italic> in murine B lineage cells leads to an alteration in transcriptome, chromatin landscape and associated transcription factor binding sites, which exhibits myeloid-like features and coincides with enhanced sensitivity to LPS induced gene expression. TFII-I deficient B cells also show increased switching to IgG3, a phenotype associated with inflammation. These results demonstrate a role for TFII-I in maintaining immune homeostasis and provide clues for <italic>GTF2I</italic> polymorphisms associated with B cell dominated autoimmune diseases in humans.</p>