Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, 138668 Singapore.
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117599 Singapore.
Sci Rep. 2017 Jan 6;7:40133. doi: 10.1038/srep40133.
Tyrosine kinase c-Abl plays an important role in early B cell development. Its deletion leads to reduced pro- and pre-B cell generation in mice. However, its function in B cell terminal differentiation remains unexplored. Here, we used c-Abl Aicda mice, in which c-Abl is ablated only in antigen-activated B cells, to study the role of c-Abl in germinal center (GC) B and antibody-secreting plasma cell formation. Upon challenge with a model antigen, we found normal GC and memory B but reduced plasma cells and antigen-specific antibody response in the mutant mice. In-vitro studies revealed that plasma cells lacking c-Abl could be generated but did not accumulate in culture, indicative of survival defect. They also exhibited impaired STAT3 phosphorylation. The plasma cell defects could be rectified by introduction of Bim-deficiency or delivery of colivelin, a STAT3 activator, into c-Abl Aicda mice. Hence, c-Abl signalling regulates the survival of plasma cells.
酪氨酸激酶 c-Abl 在早期 B 细胞发育中发挥重要作用。其缺失会导致小鼠前体和祖 B 细胞生成减少。然而，其在 B 细胞终末分化中的功能仍未被探索。在这里，我们使用仅在抗原激活的 B 细胞中缺失 c-Abl 的 c-Abl Aicda 小鼠来研究 c-Abl 在生发中心 (GC) B 细胞和分泌抗体的浆细胞形成中的作用。在受到模型抗原的刺激后，我们发现突变小鼠中的 GC 和记忆 B 细胞正常，但浆细胞和抗原特异性抗体反应减少。体外研究表明，缺乏 c-Abl 的浆细胞可以生成，但在培养中不会积累，表明存在生存缺陷。它们还表现出 STAT3 磷酸化受损。通过引入 Bim 缺陷或向 c-Abl Aicda 小鼠中递送 STAT3 激活剂 colivelin，可以纠正浆细胞缺陷。因此，c-Abl 信号通路调节浆细胞的存活。
