Halcomb Kristina E, Contreras Cristina M, Hinman Rochelle M, Coursey Terry G, Wright Heather L, Satterthwaite Anne B
Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390-8884, USA.
Eur J Immunol. 2007 Apr;37(4):1033-42. doi: 10.1002/eji.200636451.
The pre-BCR and the BCR regulate B cell development via a signalosome nucleated by the adaptor protein B cell linker protein (BLNK). Formation of this complex facilitates activation of phospholipase C (PLC) gamma2 by Bruton's tyrosine kinase (Btk). To determine whether Btk and PLCgamma2 also have separate functions, we generated Btk(-/-)PLCgamma2(-/-) mice. They demonstrated a block in development at the pre-B stage and increased pre-BCR surface expression. This phenotype was more severe than that of Btk(-/-) or PLCgamma2(-/-) mice. Although both Btk and PLCgamma2 were required for proliferation of splenic B cells in response to BCR cross-linking, they contributed differently to anti-IgM-induced phosphorylation of ERK. Btk(-/-) and PLCgamma2(-/-) mice each had a reduced frequency of Iglambda-expressing B cells and impaired migration of pre-B cells towards stromal cell-derived factor 1. However, the increase in pre-B cell malignancy that occurs in BLNK(-/-) mice in the absence of Btk was not observed in the absence of PLCgamma2. Thus, Btk and PLCgamma2 act both in concert and independently throughout B cell development.
前B细胞受体（pre-BCR）和B细胞受体（BCR）通过由衔接蛋白B细胞连接蛋白（BLNK）形成核心的信号小体来调节B细胞发育。该复合物的形成有助于布鲁顿酪氨酸激酶（Btk）激活磷脂酶C（PLC）γ2。为了确定Btk和PLCγ2是否也具有独立的功能，我们培育出了Btk(-/-)PLCγ2(-/-)小鼠。这些小鼠在前B细胞阶段的发育出现阻滞，前BCR表面表达增加。该表型比Btk(-/-)或PLCγ2(-/-)小鼠的表型更为严重。尽管Btk和PLCγ2都是脾B细胞响应BCR交联进行增殖所必需的，但它们在抗IgM诱导的细胞外信号调节激酶（ERK）磷酸化过程中的作用有所不同。Btk(-/-)和PLCγ2(-/-)小鼠表达免疫球蛋白λ（Iglambda）的B细胞频率均降低，前B细胞向基质细胞衍生因子1的迁移也受损。然而，在没有PLCγ2的情况下，并未观察到在没有Btk时BLNK(-/-)小鼠中出现的前B细胞恶性肿瘤增加的情况。因此，Btk和PLCγ2在整个B细胞发育过程中既协同作用又各自发挥独立作用。
