King L B, Monroe J G
University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Immunol Rev. 2000 Aug;176:86-104. doi: 10.1034/j.1600-065x.2000.00609.x.
The immature and transitional immature B-cell stages define an important window in B-cell development, as it is at this point that cells committed to the B-cell lineage first express the clonotypic B-cell antigen receptor (BCR) and cells expressing self-reactive specificities may be identified and eliminated. The intrinsic susceptibility of the immature B cell to negative selection following BCR engagement distinguishes these cells functionally from mature-stage B cells in which BCR cross-linking leads to activation. Our laboratory has been interested in determining the molecular events responsible for the distinct and disparate responses of immature and mature B cells to antigen receptor signaling in order to understand the molecular basis of negative selection of developing B cells. These studies have indicated that developmentally regulated mechanisms, intrinsic to the B cell, regulate the differential responsiveness of the immature and mature stage B cell to antigen. However, the "hard-wired" BCR-induced apoptotic response of the immature B cell can be modified by the microenvironmental context in which the antigen is encountered. This plasticity fine tunes the BCR-induced response of the immature B cell by regulating the mechanism of negative selection and, under defined circumstances, allowing for recruitment into an immune response.
未成熟和过渡性未成熟B细胞阶段在B细胞发育过程中定义了一个重要窗口，因为正是在这个阶段，致力于B细胞谱系的细胞首次表达克隆型B细胞抗原受体（BCR），并且表达自身反应性特异性的细胞可能会被识别和清除。未成熟B细胞在BCR结合后对阴性选择的内在敏感性在功能上使这些细胞与成熟阶段的B细胞区分开来，在成熟阶段的B细胞中，BCR交联会导致激活。我们实验室一直致力于确定导致未成熟和成熟B细胞对抗原受体信号产生不同和不同反应的分子事件，以便了解发育中B细胞阴性选择的分子基础。这些研究表明，B细胞固有的发育调节机制调节未成熟和成熟阶段B细胞对抗原的差异反应性。然而，未成熟B细胞“硬连线”的BCR诱导的凋亡反应可以被遇到抗原的微环境所改变。这种可塑性通过调节阴性选择机制来微调未成熟B细胞的BCR诱导反应，并在特定情况下允许其被招募到免疫反应中。
