The ICF2 gene Zbtb24 specifically regulates the differentiation of B1 cellsviapromoting heme synthesis

• DOI: 10.1101/2023.12.23.573176
• Publication Date: 2023-12-23T22:45:15Z
• Authors: Jun Wang; He Gao; Sai Zhao; Xiao-Qiu Dai; Xiao-Yuan Qin; Wei-Long Zheng; Can Zhu; Hong-Min Wang; Xue-Mei Zhu; Fang-Yuan Gong; Xiao-Ming Gao; Ying Zhao
• Keywords: Naive B cell

ABSTRACT Loss-of-function mutations of ZBTB24 cause the Immunodeficiency, Centromeric Instability and Facial Anomalies syndrome 2 (ICF2). ICF2 is a rare autosomal recessive disorder with immunological defects in serum antibodies circulating memory B cells, indicating an essential role terminal differentiation cells. Here we generated B-cell specific Zbtb24-deficient mice systemically investigated its cell development function both vivo vitro . Zbtb24 dispensable for & maintenance naive mice. Surprisingly, deletion does not evidently compromise germinal center reactions resulting primary secondary antibody responses induced by T-cell dependent antigens, but significantly inhibits independent antigen-elicited productions At cellular level, Zbtb24-deficiency specifically impedes plasma B1 cells without impairing their survival, activation proliferation Mechanistically, Zbtb24-ablation attenuates heme biosynthesis partially through mTORC1 addition exogenous hemin abrogates Zbtb24-null Our study suggests that defected functions may contribute to recurrent infections patients, discloses B1-specific regulating production, which relevant barrier defenses against invading pathogens.