Pillai Shiv, Cariappa Annaiah, Moran Stewart T
Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02129, USA.
Immunol Rev. 2004 Feb;197:206-18. doi: 10.1111/j.0105-2896.2003.097.x.
Although it is appreciated that the antigen receptor on B cells is required for peripheral B-lymphocyte development and survival, it has been unclear whether this receptor interacts with self-antigens during development or if it signals constitutively in an antigen-independent fashion. The analysis of mutant mice in which antigen receptor signaling in B cells is either attenuated or enhanced has revealed the existence of a follicular versus marginal zone B-lymphocyte cell-fate decision. These analyses indicate that weak antigen receptor-derived signals favor marginal zone B-cell generation, and relatively strong signals favor the development of mature follicular B cells. Even stronger signals derived from the antigen receptor favor the generation of B1 B cells. This signal strength model for B-cell development supports the notion that self-antigens of varying affinity may mediate positive selection and lineage commitment. Direct evidence supporting such a view has been obtained from the analysis of antigen receptor knockin mice. Specific antigen receptors guide B cells to develop into specific lineages. Although Notch-2, nuclear factor-kappaBp50, and other genes are essential for marginal zone B-cell development, instructive signals delivered by the antigen receptor represent the primary force driving positive selection and lineage commitment in B lymphocytes.
尽管人们认识到B细胞上的抗原受体对于外周B淋巴细胞的发育和存活是必需的，但尚不清楚该受体在发育过程中是否与自身抗原相互作用，或者它是否以抗原非依赖性方式持续发出信号。对B细胞中抗原受体信号传导减弱或增强的突变小鼠的分析揭示了滤泡性与边缘区B淋巴细胞细胞命运决定的存在。这些分析表明，源自抗原受体的微弱信号有利于边缘区B细胞的产生，而相对较强的信号有利于成熟滤泡性B细胞的发育。源自抗原受体的更强信号有利于B1 B细胞的产生。这种B细胞发育的信号强度模型支持了不同亲和力的自身抗原可能介导阳性选择和谱系定向的观点。通过对抗原受体敲入小鼠的分析获得了支持这一观点的直接证据。特定的抗原受体引导B细胞发育成特定的谱系。尽管Notch-2、核因子-κBp50和其他基因对于边缘区B细胞的发育至关重要，但抗原受体传递的指导性信号是驱动B淋巴细胞阳性选择和谱系定向的主要力量。
