Regulation of the BCR signalosome by the class II peptide editor, H2-M, affects the development and repertoire of innate-like B cells.
Regulation of the BCR signalosome by the class II peptide editor, H2-M, affects the development and repertoire of innate-like B cells.
复制标题
II 类肽编辑器 H2-M 对 BCR 信号体的调节会影响先天样 B 细胞的发育和功能。
DOI：
10.1016/j.celrep.2021.110200
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发表时间：
2022
期刊：
影响因子：
8.8
通讯作者：
Bo
中科院分区：
文献类型：
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作者：
Ghosh,Debopam;Pham,ThoD;Nanaware,PadmaP;Sengupta,Deepanwita;Adler,LitalN;Li,CaiyunG;He,Xiao;O'Mara,MaryE;Kantor,AaronB;Nguyen,KhoaD;Yang,Yang;Eisenlohr,LaurenceC;Jensen,PeterE;Herzenberg,LeonoreA;Stern,LawrenceJ;Bo
非经典的主要组织相容性复合物II类（MHCII）蛋白H2-M编辑与常规MHCII结合的肽，有利于稳定的肽/MHCII（p/MHCII）复合物。在这里，我们表明，H2-M缺陷影响B-1细胞的生存，降低细胞的更新能力，并改变免疫球蛋白库，允许选择细胞特异性高丰度表位，但不是低频表位。H2-M缺陷型B-1细胞具有较短的CDR 3长度、较高的带正电荷的氨基酸含量、较短的连接区、较低的突变频率和偏斜的克隆分布。从机制上讲，H2-M损失减少了质膜p/MHCII与B-1细胞上的B细胞受体（BCR）的结合，并降低了整合的BCR信号强度，这是B-1细胞选择、成熟和维持的关键决定因素。因此，H2-M：MHCII相互作用作为BCR信号传导的细胞内在调节剂，并影响B-1细胞克隆库的选择。
The non-classical Major Histocompatibility Complex class II (MHCII) protein, H2-M, edits peptides bound to conventional MHCII in favor of stable peptide/MHCII (p/MHCII) complexes. Here, we show that H2-M deficiency affects B-1 cell survival, reduces cell renewal capacity, and alters immunoglobulin repertoire, allowing for the selection of cells specific for highly abundant epitopes, but not low-frequency epitopes. H2-M-deficient B-1 cells have shorter CDR3 length, higher content of positively charged amino acids, shorter junctional regions, less mutation frequency, and a skewed clonal distribution. Mechanistically, H2-M loss reduces plasma membrane p/MHCII association with B cell receptors (BCR) on B-1 cells and diminishes integrated BCR signal strength, a key determinant of B-1 cell selection, maturation, and maintenance. Thus, H2-M:MHCII interaction serves as a cell-intrinsic regulator of BCR signaling and influences the selection of the B-1 cell clonal repertoire.