Chung James B, Sater Richard A, Fields Michele L, Erikson Jan, Monroe John G
Division of Rheumatology, Department of Medicine, 311 BRB II/III, 421 Curie Boulevard, University of Pennsylvania, PA 19104, USA.
Int Immunol. 2002 Feb;14(2):157-66. doi: 10.1093/intimm/14.2.157.
Transitional immature B cells undergo apoptosis and fail to proliferate in response to BCR cross-linking, thus representing a target for negative selection of potentially autoreactive B cells in vivo. In agreement with recent reports, transitional B cells were divided into developmentally contiguous subsets based on their surface expression of CD23. When transferred, CD23(+) transitional B cells readily localized to the splenic follicles and the outer PALS. Compared with CD23(-) transitional B cells, CD23(+) transitional B cells proliferated more vigorously and were rescued from BCR-induced apoptosis to a greater degree, by T cell help signals. However, both CD23(-) and CD23(+) transitional B cells failed to up-regulate CD86 (B7-2) in response to BCR ligation. These findings demonstrate that phenotypically defined subsets within the transitional B cell population are functionally distinct. Specifically, responsiveness to T cell help is a late acquisition corresponding to the stage when the B cells gain access to peripheral compartments enriched in antigen and activated T cells. The failure of transitional B cells to up-regulate CD86 to BCR-mediated stimulation suggests a unique interaction between transitional B cells and T cells with implications for tolerance in the T cell compartment.
过渡性未成熟B细胞会发生凋亡,并且在BCR交联时无法增殖,因此是体内潜在自身反应性B细胞阴性选择的一个靶点。与近期报道一致,根据CD23的表面表达情况,将过渡性B细胞分为发育上连续的亚群。转移后,CD23(+)过渡性B细胞很容易定位于脾滤泡和外周动脉淋巴鞘(PALS)外层。与CD23(-)过渡性B细胞相比,CD23(+)过渡性B细胞增殖更为活跃,并且在T细胞辅助信号作用下,能在更大程度上从BCR诱导的凋亡中被挽救。然而,CD23(-)和CD23(+)过渡性B细胞在BCR连接时均未能上调CD86(B7-2)的表达。这些发现表明,过渡性B细胞群体中表型定义的亚群在功能上是不同的。具体而言,对T细胞辅助的反应性是在B细胞进入富含抗原和活化T细胞的外周区室阶段才出现的后期特征。过渡性B细胞在BCR介导的刺激下未能上调CD86,这表明过渡性B细胞与T细胞之间存在独特的相互作用,对T细胞区室的耐受性有影响。