Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Japan.
Cell Immunol. 2010;266(1):24-31. doi: 10.1016/j.cellimm.2010.08.007.
Fc receptor-like A (FCRLA) and FCRLB have homology to the transmembrane FCRL family members (FCRL 1-6) and to the conventional receptors for the Fc portion of immunoglobulin, but uniquely are cytosolic proteins expressed in B cells. Here we describe the phenotype of Fcrlb-gene targeted mice. B cell development and in vitro responses are normal; however, antibody responses to a T-dependent antigen are elevated. The gene encoding the inhibitory FcγRIIb is located nearby Fcrlb. Although Fcrlb-gene targeting had no effect on the function or basal expression of FcγRIIb, its expression was reduced following activation. This abnormal regulation was due to co-inheritance of Fcgr2b and the mutant Fcrlb allele from the 129 ES cells. A promoter polymorphism in the 129/Sv Fcgr2b allele results in diminished upregulation of FcγRIIb following B cell activation. Thus, we speculate that the enhanced antibody response seen in the FCRLB-deficient mice may be due to the Fcgr2b promoter.
Fc 受体样 A（FCRLA）和 FCRLB 与跨膜 FCRL 家族成员（FCRL1-6）和免疫球蛋白 Fc 部分的常规受体具有同源性，但它们是独特的在 B 细胞中表达的细胞质蛋白。在这里，我们描述了 Fcrlb 基因靶向小鼠的表型。B 细胞发育和体外反应正常；然而，对 T 依赖性抗原的抗体反应升高。编码抑制性 FcγRIIb 的基因位于 Fcrlb 附近。尽管 Fcrlb 基因靶向对 FcγRIIb 的功能或基础表达没有影响，但在激活后其表达减少。这种异常调节归因于来自 129 ES 细胞的 Fcgr2b 和突变 Fcrlb 等位基因的共遗传。129/Sv Fcgr2b 等位基因中的启动子多态性导致 B 细胞激活后 FcγRIIb 的上调减少。因此，我们推测在 FCRLB 缺陷小鼠中观察到的增强的抗体反应可能归因于 Fcgr2b 启动子。
