Different nuclear signals are activated by the B cell receptor during positive versus negative signaling
Different nuclear signals are activated by the B cell receptor during positive versus negative signaling
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DOI：
10.1016/s1074-7613(00)80285-x
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发表时间：
1997-04-01
期刊：
影响因子：
32.4
通讯作者：
Goodnow, CC
中科院分区：
文献类型：
--
作者：
Healy, JI;Dolmetsch, RE;Goodnow, CC
免疫原性与致耐受性细胞应答如何通过受体如B细胞抗原受体（BCR）发出信号尚不清楚。在这里，我们比较了对外源抗原有积极反应的幼稚细胞和对自身抗原有消极反应的自身耐受细胞中的BCR信号传导。在幼稚细胞中，外源性抗原触发了Targe双相钙反应，并通过NF-AT、NF-κ B、JNK和ERK/pp 90 rsk激活核信号。在耐受性B细胞中，自身抗原刺激低钙振荡并激活NF-AT和ERK/pp 90 rsk，但不激活NF-κ B或JNK。缺乏磷酸酶CD 45的自身反应性B细胞没有表现出钙振荡或ERK/pp 90 rsk激活，也没有对自身抗原产生负性反应。这些数据揭示了在外源抗原的阳性选择和自身抗原的阴性选择过程中，BCR向细胞核的信号传导存在显著的生化差异。
It is not known how immunogenic versus tolerogenic cellular responses are signaled by receptors such as the B cell antigen receptor (BCR). Here we compare BCR signaling in naive cells that respond positively to foreign antigen and self-tolerant cells that respond negatively to self-antigen. In naive cells, foreign antigen triggered a Targe biphasic calcium response and activated nuclear signals through NF-AT, NF-kappa B, JNK, and ERK/pp90rsk. In tolerant B cells, self-antigen stimulated low calcium oscillations and activated NF-AT and ERK/pp90rsk but not NF-kappa B or JNK. Self-reactive B cells lacking the phosphatase CD45 did not exhibit calcium oscillations or ERK/pp90rsk activation, nor did they repond negatively to self-antigen. These data reveal striking biochemical differences in BCR signaling to the nucleus during positive selection by foreign antigens and negative selection by self-antigens.