Monroe John G, Dorshkind Kenneth
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Adv Immunol. 2007;95:1-50. doi: 10.1016/S0065-2776(07)95001-4.
In adult mammals, bone marrow pluripotent hematopoietic stem cells generate B lymphoid-specified progeny that progress through a series of well-characterized stages before generating B-cell receptor expressing B lymphocytes. These functionally immature B lymphocytes then migrate to the spleen wherein they differentiate through transitional stages into follicular or marginal zone B lymphocytes capable of responding to T-dependent and -independent antigens, respectively. During the terminal stages of B lymphocyte development in the bone marrow, as well as immediately following egress into the peripheral compartments, B lymphocytes are counterselected to eliminate B lymphocytes with potentially dangerous self-reactivity. These developmental and selection events in the bone marrow and periphery are dependent on the integration of intrinsic genetic programs with extrinsic microenvironmental signals that drive progenitors toward increasing B lineage commitment and maturation. This chapter provides a comprehensive overview of the various stages of primary and secondary B lymphocyte development with an emphasis on the selection processes that affect decisions at critical checkpoints. Our intent is to stress the concept that at many steps in the developmental process leading to a mature immunocompetent B lymphocyte, B lineage cells are integrating multiple and different signaling inputs that are translated into specific and appropriate cell fate decisions.
在成年哺乳动物中，骨髓多能造血干细胞产生B淋巴细胞特异性后代，这些后代在产生表达B细胞受体的B淋巴细胞之前，会经历一系列特征明确的阶段。这些功能上未成熟的B淋巴细胞随后迁移至脾脏，在那里它们通过过渡阶段分别分化为能够对T细胞依赖性和非依赖性抗原作出反应的滤泡或边缘区B淋巴细胞。在骨髓中B淋巴细胞发育的终末阶段，以及刚进入外周区室后，B淋巴细胞会被逆向选择，以清除具有潜在危险的自身反应性的B淋巴细胞。骨髓和外周的这些发育和选择事件依赖于内在遗传程序与外在微环境信号的整合，这些信号驱动祖细胞向增加B细胞谱系定向和成熟的方向发展。本章全面概述了原发性和继发性B淋巴细胞发育的各个阶段，重点是影响关键检查点决策的选择过程。我们的目的是强调这样一个概念，即在导致成熟免疫活性B淋巴细胞的发育过程中的许多步骤中，B细胞谱系细胞正在整合多种不同的信号输入，这些信号输入被转化为特定且合适的细胞命运决定。
