Abelson tyrosine kinase controls BCR signalling and B‐cell differentiation by promoting B‐cell metabolism

• Published in: Immunology Vol. 167; no. 2; pp. 181 - 196
• Main Authors: Luo, Li, Jiang, Panpan, Chen, Qianglin, Chang, Jiang, Jing, Yukai, Luo, Xi, Gu, Heng, Huang, Yanmei, Chen, Ran, Liu, Ju, Kang, Danqing, Liu, Qi, Wang, Yi, Fang, Guofeng, Zhu, Yingzi, Guan, Fei, Lei, Jiahui, Yang, Lu, Liu, Chaohong, Dai, Xin
• Format: Journal Article
• Language: English
• Published: Oxford Wiley Subscription Services, Inc 01.10.2022
• Subjects: Actin; Antigens; B-cell receptor; BCR protein; BCR signalling; B‐cell; B‐cell differentiation; B‐cell metabolism; CD19 antigen; Cell differentiation; Cell spreading; Chronic myeloid leukemia; c‐Abl; Differentiation (biology); Immunization; Inositol; Inositols; Kinases; Leukemia; Lymphocytes; Metabolic pathways; Metabolism; Mitochondria; myo-Inositol-1 (or 4)-monophosphatase; Protein-tyrosine kinase; Signal transduction; Signaling; Signalosomes; Tyrosine
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/imm.13525

As a nonreceptor tyrosine kinase, Abelson tyrosine kinase (c‐Abl) was first studied in chronic myelogenous leukaemia, and its role in lymphocytes has been well characterised. c‐Abl is involved in B‐cell development and CD19‐associated B‐cell antigen receptor (BCR) signalling. Although c‐Abl regulates different metabolic pathways, the role of c‐Abl is still unknown in B‐cell metabolism. In this study, B‐cell‐specific c‐Abl knockout (KO) mice (Mb1Cre+/−c‐Ablfl/fl) were used to investigate how c‐Abl regulates B‐cell metabolism and BCR signalling. We found that the levels of activation positive BCR signalling proximal molecules, phosphorylated spleen tyrosine kinase (pSYK) and phosphorylated Bruton tyrosine kinase (pBTK), were decreased, while the level of key negative regulator, phosphorylated SH2‐containing inositol phosphatase 1 (pSHIP1), was increased in Mb1Cre+/−c‐Ablfl/fl mice. Furthermore, we found c‐Abl deficiency weakened the B‐cell spreading, formation of BCR signalosomes, and the polymerisation of actin during BCR activation, and also impaired the differentiation of germinal center (GC) B‐cells both in quiescent condition and after immunisation. Moreover, B‐cell mitochondrial respiration and the expression of B‐cell metabolism‐regulating molecules were downregulated in c‐Abl deficiency mice. Overall, c‐Abl, which involved in actin remodelling and B‐cell metabolism, positively regulates BCR signalling and promotes GC differentiation. Abelson tyrosine kinase(c‐Abl) can promote B‐cell spreading, formation of BCR signalosomes, and the polymerisation of actin during BCR activation. The deficiency of c‐Abl impaired the differentiation of germinal center (GC) B‐cells both in quiescent condition and after immunisation. Moreover, B‐cell mitochondrial respiration and the expression of B‐cell metabolism‐regulating molecules were downregulated in c‐Abl deficiency mice. Overall, c‐Abl, which involved in actin remodelling and B‐cell metabolism, positively regulates BCR signalling and promotes GC differentiation.