The B cell receptor promotes B cell activation and proliferation through a non-ITAM tyrosine in the Igα cytoplasmic domain
The B cell receptor promotes B cell activation and proliferation through a non-ITAM tyrosine in the Igα cytoplasmic domain
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DOI：
10.1016/j.immuni.2006.04.014
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发表时间：
2006-07-01
期刊：
影响因子：
32.4
通讯作者：
Rajewsky, Klaus
中科院分区：
文献类型：
--
作者：
Patterson, Heide Christine K.;Kraus, Manfred;Rajewsky, Klaus
除了基于IG α和β免疫受体酪氨酸的激活基序（ITAM）的酪氨酸之外，进化上保守的IG α非ITAM酪氨酸204在抗原被B细胞受体（BCR）识别后变得磷酸化。在这里，我们证明了来自IG α Y204靶向突变小鼠的脾B细胞在BCR接合时表现出T细胞非依赖性B细胞活化、增殖和抗体应答的孤立缺陷，但BCR加帽、抗原内化、抗原呈递和T细胞依赖性抗体产生正常。正常数量的突变型B细胞显示BCR诱导的脾酪氨酸激酶（Syk）磷酸化未受损，但B细胞连接蛋白（BLNK）磷酸化、钙流和核因子κ B（NF κ B）、c-jun N末端激酶（JNK）和细胞外信号调节激酶（ERK）活化减少。这些结果表明，IG α非ITAM酪氨酸204通过衔接子BLNK的磷酸化促进了独特的细胞应答，即T-非依赖性B细胞增殖和分化。
In addition to the tyrosines of the Ig alpha and beta immunoreceptor tyrosine-based activation motifs (ITAMs), the evolutionarily conserved Ig alpha non-ITAM tyrosine 204 becomes phosphorylated upon antigen recognition by the B cell receptor (BCR). Here we demonstrate that splenic B cells from mice with a targeted mutation of Ig alpha Y204 exhibited an isolated defect in T cell-independent B cell activation, proliferation, and antibody response upon BCR engagement, yet normal BCR capping, antigen internalization, antigen presentation, and T cell-dependent antibody production. Mutant B cells, present in normal numbers, exhibited unimpaired BCR-induced spleen tyrosine kinase (Syk) phosphorylation but reduced B cell linker protein (BLNK) phosphorylation, calcium flux, and nuclear factor kappa B (NF kappa B), c-jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) activation. These results suggest that Ig alpha non-ITAM tyrosine 204 promotes a distinct cellular response, namely T-independent B cell proliferation and differentiation via phosphorylation of the adaptor BLNK.