Xu Zhiwei, Butfiloski Edward J, Sobel Eric S, Morel Laurence
Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, 1600 Archer Road, Gainesville, FL 32610, USA.
J Immunol. 2004 Nov 15;173(10):6050-8. doi: 10.4049/jimmunol.173.10.6050.
The abundance of B-1a cells found in the peritoneal cavity of mice is under genetic control. The lupus-prone mouse New Zealand Black and New Zealand White (NZB x NZW)F(1) and its derivative NZM2410 are among the strains with the highest numbers of peritoneal B1-a cells. We have previously identified an NZM2410 genetic locus, Sle2, which is associated with the production of large numbers of B-1a cells. In this paper, we examined the mechanisms responsible for this phenotype by comparing congenic C57BL/6 mice with or without Sle2. Fetal livers generated more B-1a cells in B6.Sle2 mice, providing them with a greater starting number of B-1a cells early in life. Sle2-expressing B1-a cells proliferated significantly more in vivo than their B6 counterparts, and reciprocal adoptive transfers showed that this phenotype is intrinsic to Sle2 peritoneal B cells. The rate of apoptosis detected was significantly lower in B6.Sle2 peritoneal cavity B-1a cells than in B6, with or without exogenous B cell receptor cross-linking. Increased proliferation and decreased apoptosis did not affect Sle2 peritoneal B-2 cells. In addition, a significant number of peritoneal cavity B-1a cells were recovered in lethally irradiated B6.Sle2 mice reconstituted with B6.Igh(a) bone marrow, showing radiation resistance in Sle2 B-1a cells or its precursors. Finally, B6.Sle2 adult bone marrow and spleen were a significant source of peritoneal B-1a cells when transferred into B6.Rag2(-/-) mice. This suggests that peritoneal B-1a cells are replenished throughout the animal life span in B6.Sle2 mice. These results show that Sle2 regulates the size of the B-1a cell compartment at multiple developmental checkpoints.
在小鼠腹腔中发现的B-1a细胞数量受基因控制。易患狼疮的小鼠品系新西兰黑鼠和新西兰白鼠（NZB×NZW）F1及其衍生品系NZM2410是腹腔B1-a细胞数量最多的品系之一。我们之前鉴定出一个NZM2410基因座Sle2，它与大量B-1a细胞的产生有关。在本文中，我们通过比较带有或不带有Sle2的同源C57BL/6小鼠，研究了导致这种表型的机制。B6.Sle2小鼠的胎肝产生了更多的B-1a细胞，使它们在生命早期就拥有更多数量的起始B-1a细胞。表达Sle2的B1-a细胞在体内的增殖明显多于其B6对应细胞，相互过继转移表明这种表型是Sle2腹膜B细胞所固有的。无论有无外源性B细胞受体交联，检测到的B6.Sle2腹腔B-1a细胞凋亡率均显著低于B6。增殖增加和凋亡减少并未影响Sle2腹膜B-2细胞。此外，在用B6.Igh(a)骨髓重建的经致死性照射的B6.Sle2小鼠中，回收了大量腹腔B-1a细胞，表明Sle2 B-1a细胞或其前体细胞具有辐射抗性。最后，当将B6.Sle2成年骨髓和脾脏转移到B6.Rag2(-/-)小鼠中时，它们是腹腔B-1a细胞的重要来源。这表明在B6.Sle2小鼠中，腹腔B-1a细胞在动物的整个生命周期中都得到补充。这些结果表明，Sle2在多个发育检查点调节B-1a细胞区室的大小。
