As the unique source of diverse immunoglobulin repertoires, B lymphocytes are an indispensable part of humoral immunity. B cell progenitors progress through sequential and mutually exclusive states of proliferation and recombination, coordinated by cytokines and chemokines. Mutations affecting the crucial pre-B cell checkpoint result in immunodeficiency, autoimmunity, and leukemia. This checkpoint was previously modeled by the signaling of two opposing receptors, IL-7R and the pre-BCR. We provide an update to this model in which three receptors, IL-7R, pre-BCR, and CXCR4, work in concert to coordinate both the proper positioning of B cell progenitors in the bone marrow (BM) microenvironment and their progression through the pre-B checkpoint. Furthermore, signaling initiated by all three receptors directly instructs cell fate and developmental progression.

作为多种免疫球蛋白库的独特来源，B淋巴细胞是体液免疫必不可少的部分。B细胞祖细胞在细胞因子和趋化因子的协调下，通过依次和互斥的增殖和重组状态而发展。影响关键的B前细胞检查点的突变会导致免疫缺陷，自身免疫和白血病。该检查点以前是通过两个相对的受体IL-7R和pre-BCR的信号传导来建模的。我们提供了此模型的更新，其中三个受体IL-7R，pre-BCR和CXCR4协同工作，以协调B细胞祖细胞在骨髓（BM）微环境中的正确定位以及它们在整个前期的进程-B检查点。此外，