Integrated Department of Immunology, University of Colorado School of Medicine, National Jewish Health, Denver, CO, USA.
Immunol Res. 2013 Mar;55(1-3):231-40. doi: 10.1007/s12026-012-8366-7.
Immature B cells are generated daily in the bone marrow tissue. More than half of the newly generated immature B cells are autoreactive and bind a self-antigen, while the others are nonautoreactive. A selection process has evolved on the one hand to thwart development of autoreactive immature B cells and, on the other hand, to promote further differentiation of nonautoreactive immature B cells into transitional and mature B cells. These negative and positive selection events are carefully regulated by signals that emanate from the antigen receptor, whether antigen-mediated or tonic, and are influenced by signals that are generated by receptors that bind cytokines, chemokines, and other factors produced in the bone marrow tissue. These signals, therefore, are the predominant driving forces for the generation of a B cell population that is capable of protecting the body from infections while maintaining self-tolerance. Here, we review recent findings from our group and others that describe how tonic antigen receptor signaling and bone marrow cytokines regulate the selection of immature B cells.
未成熟 B 细胞每天在骨髓组织中产生。超过一半的新生成的未成熟 B 细胞是自身反应性的，与自身抗原结合，而其余的是非自身反应性的。一方面，已经进化出一个选择过程来阻止自身反应性未成熟 B 细胞的发育，另一方面，促进非自身反应性未成熟 B 细胞进一步分化为过渡性和成熟 B 细胞。这些阴性和阳性选择事件受到来自抗原受体的信号的精细调节，无论是抗原介导的还是持续的，并且受到结合细胞因子、趋化因子和其他在骨髓组织中产生的因子的受体产生的信号的影响。因此，这些信号是产生能够保护身体免受感染同时保持自身耐受的 B 细胞群体的主要驱动力。在这里，我们回顾了我们小组和其他小组的最新发现，这些发现描述了持续的抗原受体信号和骨髓细胞因子如何调节未成熟 B 细胞的选择。
