The unique antigen receptor signaling phenotype of B-1 cells is influenced by locale but induced by antigen
The unique antigen receptor signaling phenotype of B-1 cells is influenced by locale but induced by antigen
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DOI：
10.4049/jimmunol.169.4.1735
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发表时间：
2002-08-15
影响因子：
4.4
通讯作者：
Cambier, JC
中科院分区：
文献类型：
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作者：
Chumley, MJ;Dal Porto, JM;Cambier, JC
正常动物含有一种自身反应性B淋巴细胞亚群，即B-1亚群，该亚群受未知机制的控制，以防止自身免疫。使用V(H)11V(Kappa)9Ig转基因小鼠，具有该亚群的特异性原型，我们探索了导致这些细胞先前报道的Ag低反应的条件。我们报告腹膜V(H)11V(Kappa)9B细胞表现出典型的B-1行为。基础细胞内游离钙离子浓度高，受体介导的钙离子动员可忽略不计。然而，这只小鼠的脾B细胞，虽然表型类似于它们的腹膜对应细胞，包括CD5的表达，但通过钙内流和改变的酪氨酸磷酸化反应来测量对Ag的强健的B-2样反应。当这些脾细胞过继地转移到腹膜腔并遇到它们的同源自身抗原时，它们获得了B-1信号表型。随之而来的低反应性的特征是基础细胞内钙和静息酪氨酸磷酸化水平的增加，并突出表现为明显取消了B细胞受体介导的钙动员。因此，我们表明，在特定的微环境中，如腹膜，以及我们建议的其他特权部位，自我抗原识别在激活的B细胞上赋予了一种独特的形式的无能。这可能解释了为什么在避免自身免疫的同时，自身反应性B-1细胞能够存在。
Normal animals contain an autoreactive B lymphocyte subset, the B-1 subset, which is controlled by undefined mechanisms to prevent autoimmunity. Using a V(H)11V(kappa)9 Ig transgenic mouse, with a specificity prototypic of the subset, we have explored conditions responsible for the previously reported Ag hyporesponsiveness of these cells. We report that peritoneal V(H)11V(kappa)9 B cells exhibit typical B-1 behavior. with high basal intracellular free Ca2+ and negligible receptor-mediated calcium mobilization. However, splenic B cells from this mouse, while phenotypically similar to their peritoneal counterparts, including expression of CD5, mount robust B-2-like responses to Ag as measured by calcium influx and altered tyrosine phosphorylation responses. When these splenic cells are adoptively transferred to the peritoneal cavity and encounter their cognate self-Ag, they acquire a B-1 signaling phenotype. The ensuing hyporesponsiveness is characterized by increases in both basal intracellular calcium and resting tyrosyl phosphorylation levels and is highlighted by a marked abrogation of B cell receptor-mediated calcium mobilization. Thus, we show that self-Ag recognition in specific microenvironments such as the peritoneum, and we would propose other privileged sites, confers a unique form of anergy on activated B cells. This may explain how autoreactive B-1 cells can exist while autoimmunity is avoided.