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

ABSTRACT: 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 Fc?RIIb is located nearby Fcrlb. Although Fcrlb-gene targeting had no effect on the function or basal expression of Fc?RIIb, 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 Fc?RIIb 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.

SUBMITTER: Masuda K

PROVIDER: S-EPMC2995445 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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

Masuda Keiji K Mori Hiromi H Ohara Osamu O Nakayama Manabu M Wang Ji-Yang JY Burrows Peter D PD

Cellular immunology 20100101 1

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 ...[more]

PMID: 20869045

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Project description:The defect on Fc gamma receptor IIb (Fc?RIIb), the only inhibitory Fc?R, has been identified as one of the genetic factors increasing susceptibility to lupus. The prevalence of Helicobacter pylori (HP) and Fc?RIIb dysfunction-polymorphisms are high among Asians, and their co-existence is possible. Unfortunately, the influence of HP against lupus progression in patients with lupus is still controversial. In this study, the interactions between these conditions were tested with HP infection in 24-week-old Fc?RIIb-/- mice (symptomatic lupus). HP induced failure to thrive, increased stomach bacterial burdens and stomach injury (histology and cytokines) in both wild-type and Fc?RIIb-/- mice. While the severity of HP infection, as determined by these parameters, was not different between both strains, antibodies production (anti-HP, anti-dsDNA and serum gammaglobulin) were higher in Fc?RIIb-/- mice compared to wild-type. Accordingly, HP infection also accelerated the severity of lupus as determined by proteinuria, serum creatinine, serum cytokines, renal histology, and renal immune complex deposition. Although HP increased serum cytokines in both wild-type and Fc?RIIb-/- mice, the levels were higher in Fc?RIIb-/- mice. As such, HP also increased spleen weight and induced several splenic immune cells responsible for antibody productions (activated B cell, plasma cell and follicular helper T cell) in Fc?RIIb-/- mice, but not in wild-type. These data describe the different systemic responses against localized HP infection from diverse host genetic background. In conclusion, the mutual interactions between HP and lupus manifestations of Fc?RIIb-/-mice were demonstrated in this study. With the prominent immune responses from the loss of inhibitory signaling in Fc?RIIb-/- mice, HP infection in these mice induced intense chronic inflammation, increased antibody production, and enhanced lupus severity. Thus, the increased systemic inflammatory responses due to localized HP inducing gastritis in some patients with lupus may enhance lupus progression. More studies are needed.

Dataset Information

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

Publications

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

Similar Datasets

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