Suppression of autoimmunity by B lymphocyte membrane protein CD72

B细胞膜蛋白CD72的c型凝集素样结构域（CTLD）被认为与自身免疫性疾病的发生有关。然而，其CTLD的聚糖配体及其功能尚不清楚。本研究利用CD72重组蛋白，通过多糖阵列筛选，鉴定了几种磺化聚糖为CD72配体。有趣的是，一些鉴定的CD72配体是自身免疫性疾病相关抗原。此外，通过使用np -偶联CD72配体和np -偶联BSA分析CD72配体对QM小鼠和QM CD72缺陷小鼠原代B细胞中B细胞抗原受体（BCR）信号传导的影响，发现CD72配体结合含CD72配体的抗原后，BCR信号传导的CD72依赖性降低。此外，C57BL/6 CD72缺陷小鼠血清抗CD72配体IgM类抗体的含量较C57BL/6小鼠升高。这些结果提示了B细胞通过CD72-CD72配体相互作用介导的BCR信号抑制和针对含CD72配体抗原的抗体产生的新的自我和非自我识别机制。

C-type lectin-like domain (CTLD) of B cell membrane protein CD72 is suggested to associated with development of autoimmune diseases. However, the glycan ligand and function of its CTLD is not clear. In this study, some kinds of sulfated glycans were identified as CD72 ligands by glycan array screening using CD72 recombinant protein.Interestingly, some of the identified CD72 ligands are autoimmune disease-associated antigens. In addition, the effect of CD72 ligand on B cell antigen receptor (BCR) signaling in primary B cells from QM mice and QM CD72 deficient mice by analyzing calcium influx using NP-conjugated CD72 ligand and NP-conjugated BSA, showed CD72-dependent reduction of BCR signaling following ligation of CD72 ligand-containing antigen. Moreover, the amount of serum anti-CD72 ligand IgM classantibody was increased in C57BL/6 CD72 deficient mice compared with that in C57BL/6 mice. These results suggest novel self and non-self recognition mechanism of B cells by CD72-CD72 ligand interaction-mediated suppression of BCR signaling and antibody production against CD72 ligand-containing antigens.