Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
J Immunol. 2013 Jun 1;190(11):5559-66. doi: 10.4049/jimmunol.1102503. Epub 2013 Apr 29.
VH replacement provides a unique RAG-mediated recombination mechanism to edit nonfunctional IgH genes or IgH genes encoding self-reactive BCRs and contributes to the diversification of Ab repertoire in the mouse and human. Currently, it is not clear how VH replacement is regulated during early B lineage cell development. In this article, we show that cross-linking BCRs induces VH replacement in human EU12 μHC(+) cells and in the newly emigrated immature B cells purified from peripheral blood of healthy donors or tonsillar samples. BCR signaling-induced VH replacement is dependent on the activation of Syk and Src kinases but is inhibited by CD19 costimulation, presumably through activation of the PI3K pathway. These results show that VH replacement is regulated by BCR-mediated signaling in human immature B cells, which can be modulated by physiological and pharmacological treatments.
VH 替换提供了一种独特的 RAG 介导的重组机制，用于编辑无功能的 IgH 基因或编码自身反应性 BCR 的 IgH 基因，并有助于小鼠和人类中 Ab 库的多样化。目前，尚不清楚 VH 替换在早期 B 细胞谱系细胞发育过程中是如何被调控的。在本文中，我们表明，BCR 的交联诱导人 EU12 μHC(+)细胞和从健康供体的外周血或扁桃体样本中纯化的新迁出的未成熟 B 细胞中的 VH 替换。BCR 信号诱导的 VH 替换依赖于 Syk 和 Src 激酶的激活，但被 CD19 共刺激抑制，可能是通过激活 PI3K 途径。这些结果表明，VH 替换在人类未成熟 B 细胞中受到 BCR 介导的信号的调控，并且可以通过生理和药理学处理进行调节。
