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BMC Immunology

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Open Access 01-12-2012 | Research article

Human CD72 splicing isoform responsible for resistance to systemic lupus erythematosus regulates serum immunoglobulin level and is localized in endoplasmic reticulum

Authors: Yuki Hitomi, Takahiro Adachi, Naoyuki Tsuchiya, Zen-Ichiro Honda, Katsushi Tokunaga, Takeshi Tsubata

Published in: BMC Immunology | Issue 1/2012

Abstract

Background

CD72 is an inhibitory co-receptor expressed on B cells. We previously demonstrated significant association of the polymorphism of the CD72 gene with susceptibility to human systemic lupus erythematosus (SLE) in individuals carrying a SLE-susceptible FCGR2B genotype (FCGR2B-232Thr/Thr). The human CD72 locus generates a splicing isoform that lacks exon 8 (CD72Δex8) as well as full-length CD72 (CD72fl), and the CD72 polymorphism regulates exon 8 skipping.

Results

Here we demonstrated that individuals carrying the disease-protective CD72 genotype exhibit significantly lower serum immunoglobulin levels than do individuals carrying other CD72 genotypes (P < 0.05). Although expression level of CD72fl in the peripheral blood B cells was similar regardless of CD72 genotype, the protein level of CD72Δex8 was increased in individuals carrying the disease-protective CD72 genotype, suggesting a crucial role of CD72Δex8 in regulation of antibody production. By expressing these human CD72 isoforms in mouse cell lines, we further demonstrated that CD72Δex8 is accumulated in endoplasmic reticulum (ER) and fails to regulate BCR signaling whereas human CD72fl is efficiently transported to the cell surface and inhibits signaling through the B cell antigen receptor (BCR), as is the case for mouse CD72.

Conclusion

Human CD72 polymorphism appears to regulate antibody production as well as susceptibility to SLE by regulating expression of ER-localizing CD72Δex8.

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Title: Human CD72 splicing isoform responsible for resistance to systemic lupus erythematosus regulates serum immunoglobulin level and is localized in endoplasmic reticulum
Authors: Yuki Hitomi
Takahiro Adachi
Naoyuki Tsuchiya
Zen-Ichiro Honda
Katsushi Tokunaga
Takeshi Tsubata
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: BMC Immunology / Issue 1/2012
Electronic ISSN: 1471-2172
DOI: https://doi.org/10.1186/1471-2172-13-72

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Abstract

Background

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Conclusion

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