Igarashi H, Kuwahara K, Nomura J, Matsuda A, Kikuchi K, Inui S, Sakaguchi N
Department of Immunology, School of Life Science, Faculty of Medicine, Tottori University, Yonago, Japan.
J Immunol. 1994 Sep 15;153(6):2381-93.
Ig receptor (IgR) on the surface of B cells mediates the Ag-specific stimulatory signal for B cell proliferation and differentiation. In immature B cells, the stimulatory signal causes an inhibitory effect which is believed to be a key phenomenon in B cell tolerance or B cell anergy. Here, we studied the molecular mechanism of the inhibitory response of the IgR-mediated signal transduction that results in the programmed cell death of immature B cells. To analyze the downstream molecules of the IgR-mediated signal transduction, we prepared a mAb against a 160-kDa membrane protein (p160) that can coprecipitate the kinase molecule(s) acting on serine, threonine, and tyrosine residues. Anti-IgR stimulation induces the increase of the kinase activity coprecipitated with the p160 protein in mature B cell BAL17 and normal adult spleen B cells. This result suggest that the p160-associated kinase activity is one of the downstream events of the IgR-mediated signal transduction cascade. Interestingly, immature B cell lymphoma WEHI-231 and the neonatal spleen B cells showed the adverse reaction of the p160-associated kinase which results in the transient loss of the kinase activity. Moreover, the transient decrease of the p160-associated kinase was caused by the tyrosine phosphatase activity induced by the stimulation of IgR in WEHI-231. The results suggest that this molecular difference in the downstream events of the IgR-mediated signal transduction between immature B cells and mature B cells already begins at the transmembrane level in the IgR-mediated signal transduction pathway.
B细胞表面的免疫球蛋白受体（IgR）介导B细胞增殖和分化的抗原特异性刺激信号。在未成熟B细胞中，该刺激信号会产生抑制作用，这被认为是B细胞耐受性或B细胞无反应性的关键现象。在此，我们研究了IgR介导的信号转导抑制反应导致未成熟B细胞程序性细胞死亡的分子机制。为了分析IgR介导的信号转导的下游分子，我们制备了一种针对160 kDa膜蛋白（p160）的单克隆抗体，该蛋白可共沉淀作用于丝氨酸、苏氨酸和酪氨酸残基的激酶分子。抗IgR刺激可诱导成熟B细胞BAL17和正常成年脾脏B细胞中与p160蛋白共沉淀的激酶活性增加。这一结果表明，p160相关激酶活性是IgR介导的信号转导级联反应的下游事件之一。有趣的是，未成熟B细胞淋巴瘤WEHI-231和新生脾脏B细胞显示出p160相关激酶的不良反应，导致激酶活性短暂丧失。此外，WEHI-231中IgR刺激诱导的酪氨酸磷酸酶活性导致p160相关激酶的短暂降低。结果表明，未成熟B细胞和成熟B细胞在IgR介导的信号转导下游事件中的这种分子差异在IgR介导的信号转导途径的跨膜水平就已开始。
