Chalupny N J, Kanner S B, Schieven G L, Wee S F, Gilliland L K, Aruffo A, Ledbetter J A
Bristol-Myers Squibb, Pharmaceutical Research Institute, Seattle, WA 98121.
EMBO J. 1993 Jul;12(7):2691-6. doi: 10.1002/j.1460-2075.1993.tb05930.x.
Cross-linking of B cell surface immunoglobulins (sIg) results in activation of mature B cells and stimulates a molecular signaling mechanism for antigen-specific B cell expansion and differentiation. This signaling pathway is dependent on tyrosine (Tyr) phosphorylation and results in the activation of sIg-associated src family kinases and p72SYK. Rapid Tyr phosphorylation occurs on multiple protein substrates. Here we show that activation of B cells by cross-linking sIg results in an increase in Tyr phosphorylation of the lineage-restricted B cell surface antigen CD19, and show that it is a major substrate of activated Tyr kinase following sIg stimulation. Lower levels of constitutive CD19 Tyr phosphorylation occurred in most sIg+ mature B cell lines examined and in normal dense tonsillar B cells. We also find that when CD19 is Tyr-phosphorylated it becomes competent to interact with SH2 domains suggesting a mechanism whereby, following B cell activation, CD19 could be linked to intracellular signaling pathways. In sIg- pre-B cell lines, CD19 was expressed but was not constitutively phosphorylated on tyrosine. Upon CD19 cross-linking, Tyr phosphorylation of CD19 was induced in sIg- pre-B cell lines. CD19 cross-linking also directly induced Tyr phosphorylation of CD19 and other substrates in mature B cells. The ability of CD19 to signal in the absence of sIg expression may provide important stimulation in pre-B cell development.
B细胞表面免疫球蛋白（sIg）的交联导致成熟B细胞活化，并刺激抗原特异性B细胞扩增和分化的分子信号传导机制。该信号通路依赖于酪氨酸（Tyr）磷酸化，并导致sIg相关的src家族激酶和p72SYK活化。快速的Tyr磷酸化发生在多种蛋白质底物上。在这里，我们表明通过交联sIg激活B细胞会导致谱系限制性B细胞表面抗原CD19的Tyr磷酸化增加，并表明它是sIg刺激后活化Tyr激酶的主要底物。在大多数检测的sIg +成熟B细胞系和正常密集扁桃体B细胞中，组成性CD19 Tyr磷酸化水平较低。我们还发现，当CD19被Tyr磷酸化时，它能够与SH2结构域相互作用，这表明一种机制，即B细胞活化后，CD19可以与细胞内信号通路相连。在sIg -前B细胞系中，CD19表达，但酪氨酸上没有组成性磷酸化。在CD19交联后，sIg -前B细胞系中诱导了CD19的Tyr磷酸化。CD19交联还直接诱导成熟B细胞中CD19和其他底物的Tyr磷酸化。CD19在没有sIg表达的情况下发出信号的能力可能在前B细胞发育中提供重要的刺激。
