2025-04-19 九州大学
<関連情報>
- https://www.kyushu-u.ac.jp/ja/researches/view/1244
- https://www.kyushu-u.ac.jp/f/61388/24_0419_01.pdf
- https://www.science.org/doi/10.1126/sciadv.adt8199
加齢と自己免疫におけるアレルギー性B細胞の加齢性B細胞への分化における慢性BCRシグナルの重要な役割 Critical roles of chronic BCR signaling in the differentiation of anergic B cells into age-associated B cells in aging and autoimmunity
Keisuke Imabayashi, Yutaro Yada, Kazuhiko Kawata, Motoki Yoshimura, […], and Yoshihiro Baba
Science Advances Published:18 Apr 2025
DOI:https://doi.org/10.1126/sciadv.adt8199
Abstract
Age-associated B cells (ABCs) with autoreactive properties accumulate with age and expand prematurely in autoimmune diseases. However, the mechanisms behind ABC generation and maintenance remain poorly understood. We show that continuous B cell receptor (BCR) signaling is essential for ABC development from anergic B cells in aged and autoimmune mice. ABCs exhibit constitutive BCR activation, with surface BCRs being internalized. Notably, anergic B cells, but not nonautoreactive B cells, contributed to ABC formation in these models. Anergic B cells also showed a greater propensity for in vitro differentiation into ABCs, which was inhibited by the expression of the transcription factor Nr4a1. Bruton’s tyrosine kinase (Btk), a key BCR signaling component, was constitutively activated in ABCs from aged and autoimmune mice as well as patients with lupus. Inhibiting Btk reduced ABC numbers and ameliorated the pathogenicity of lupus mice. Our findings reveal critical mechanisms underlying ABC development and offer previously unrecognized therapeutic insights for autoimmune diseases.
