Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Illinois 60637, USA.
Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
Nat Rev Immunol. 2014 Feb;14(2):69-80. doi: 10.1038/nri3570. Epub 2013 Dec 31.
The development of B cells is dependent on the sequential DNA rearrangement of immunoglobulin loci that encode subunits of the B cell receptor. The pathway navigates a crucial checkpoint that ensures expression of a signalling-competent immunoglobulin heavy chain before commitment to rearrangement and expression of an immunoglobulin light chain. The checkpoint segregates proliferation of pre-B cells from immunoglobulin light chain recombination and their differentiation into B cells. Recent advances have revealed the molecular circuitry that controls two rival signalling systems, namely the interleukin-7 (IL-7) receptor and the pre-B cell receptor, to ensure that proliferation and immunoglobulin recombination are mutually exclusive, thereby maintaining genomic integrity during B cell development.
B 细胞的发育依赖于免疫球蛋白基因座的顺序 DNA 重排,这些基因座编码 B 细胞受体的亚基。该途径导航一个关键的检查点,该检查点确保在 commitment 进行重排和免疫球蛋白轻链表达之前,表达信号 competent 的免疫球蛋白重链。该检查点将前 B 细胞的增殖与免疫球蛋白轻链重组及其分化为 B 细胞区分开来。最近的进展揭示了控制两个竞争信号系统(即白细胞介素-7(IL-7)受体和前 B 细胞受体)的分子电路,以确保增殖和免疫球蛋白重组是相互排斥的,从而在 B 细胞发育过程中保持基因组完整性。