Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk 37673, Republic of Korea.
Department of Immunology, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea.
Cell Rep. 2022 Feb 15;38(7):110386. doi: 10.1016/j.celrep.2022.110386.
B-1 cell development mainly occurs via fetal and neonatal hematopoiesis and is suppressed in adult bone marrow hematopoiesis. However, little is known about the factors inhibiting B-1 cell development at the adult stage. We report that capicua (CIC) suppresses postnatal B-1a cell development and survival. CIC levels are high in B-1a cells and gradually increase in transitional B-1a (TrB-1a) cells with age. B-cell-specific Cic-null mice exhibit expansion of the B-1a cell population and a gradual increase in TrB-1a cell frequency with age but attenuated B-2 cell development. CIC deficiency enhances B cell receptor (BCR) signaling in transitional B cells and B-1a cell viability. Mechanistically, CIC-deficiency-mediated Per2 derepression upregulates Bhlhe41 levels by inhibiting CRY-mediated transcriptional repression for Bhlhe41, consequently promoting B-1a cell formation in Cic-null mice. Taken together, CIC is a key transcription factor that limits the B-1a cell population at the adult stage and balances B-1 versus B-2 cell formation.
B-1 细胞的发育主要发生在胎儿和新生儿造血过程中，并在成年骨髓造血中受到抑制。然而，关于在成年阶段抑制 B-1 细胞发育的因素知之甚少。我们报告称，capicua（CIC）抑制了产后 B-1a 细胞的发育和存活。CIC 在 B-1a 细胞中的水平较高，并随着年龄的增长逐渐增加在过渡 B-1a（TrB-1a）细胞中。B 细胞特异性 Cic-/- 小鼠表现出 B-1a 细胞群体的扩张和 TrB-1a 细胞频率的逐渐增加，但 B-2 细胞的发育减弱。CIC 缺乏增强了过渡 B 细胞和 B-1a 细胞中的 B 细胞受体（BCR）信号传导。在机制上，CIC 缺乏介导的 Per2 去抑制通过抑制 CRY 介导的转录抑制来上调 Bhlhe41 水平，从而促进 Cic-/- 小鼠中 B-1a 细胞的形成。总之，CIC 是一种关键的转录因子，它限制了成年阶段 B-1a 细胞群体的数量，并平衡了 B-1 与 B-2 细胞的形成。
