Defining the immunological phenotype of Fc receptor-like B (FCRLB) deficient mice: Confounding role of the inhibitory FcγRIIb.

Defining the immunological phenotype of Fc receptor-like B (FCRLB) deficient mice: Confounding role of the inhibitory FcγRIIb.
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DOI:
10.1016/j.cellimm.2010.08.007
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发表时间:
2010
影响因子:
4.3
通讯作者:
Burrows, Peter D.
Burrows, Peter D.
中科院分区:
医学4区
文献类型:
--
作者:
Masuda, Keiji;Mori, Hiromi;Ohara, Osamu;Nakayama, Manabu;Wang, Ji-Yang;Burrows, Peter D.

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Fc受体样A(FCRLA)和FCRLB与跨膜FCRL家族成员(FCRL 1 -6)和免疫球蛋白Fc部分的常规受体具有同源性,但独特地是在B细胞中表达的胞质蛋白。在这里,我们描述了Fcrlb基因靶向小鼠的表型。B细胞发育和体外应答正常;然而,对T依赖性抗原的抗体应答升高。编码抑制性FcγRIIb的基因位于Fcrlb附近。尽管Fcrlb基因靶向对Fe γRIIb的功能或基础表达没有影响,但其表达在激活后减少。这种异常调节是由于来自129个ES细胞的Fcgr 2b和突变的Fcrlb等位基因的共遗传。129/Sv Fcgr 2 B等位基因的启动子多态性导致B细胞活化后FcγRIIb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应答可能是由于Fcgr 2b启动子。
Fc receptor-like A (FCRLA) and FCRLB have homology to the transmembrane FCRL family members (FCRL1–6) 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.
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