Human CD72 splicing isoform responsible for resistance to systemic lupus erythematosus regulates serum immunoglobulin level and is localized in endoplasmic reticulum
<p>Abstract</p> <p>Background</p> <p>CD72 is an inhibitory co-receptor expressed on B cells. We previously demonstrated significant association of the polymorphism of the <it>CD72</it> gene with susceptibility to human systemic lupus erythematosus (SLE) in i...
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| Format: | Article |
| Language: | English |
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BMC
2012-12-01
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| Series: | BMC Immunology |
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| Online Access: | http://www.biomedcentral.com/1471-2172/13/72 |
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| author | Hitomi Yuki Adachi Takahiro Tsuchiya Naoyuki Honda Zen-Ichiro Tokunaga Katsushi Tsubata Takeshi |
| author_facet | Hitomi Yuki Adachi Takahiro Tsuchiya Naoyuki Honda Zen-Ichiro Tokunaga Katsushi Tsubata Takeshi |
| author_sort | Hitomi Yuki |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>CD72 is an inhibitory co-receptor expressed on B cells. We previously demonstrated significant association of the polymorphism of the <it>CD72</it> gene with susceptibility to human systemic lupus erythematosus (SLE) in individuals carrying a SLE-susceptible <it>FCGR2B</it> genotype (<it>FCGR2B-232Thr/Thr</it>). The human <it>CD72</it> locus generates a splicing isoform that lacks exon 8 (CD72Δex8) as well as full-length CD72 (CD72fl), and the <it>CD72</it> polymorphism regulates exon 8 skipping.</p> <p>Results</p> <p>Here we demonstrated that individuals carrying the disease-protective <it>CD72</it> genotype exhibit significantly lower serum immunoglobulin levels than do individuals carrying other <it>CD72</it> genotypes (<it>P</it> < 0.05). Although expression level of CD72fl in the peripheral blood B cells was similar regardless of <it>CD72</it> genotype, the protein level of CD72Δex8 was increased in individuals carrying the disease-protective <it>CD72</it> 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.</p> <p>Conclusion</p> <p>Human <it>CD72</it> polymorphism appears to regulate antibody production as well as susceptibility to SLE by regulating expression of ER-localizing CD72Δex8.</p> |
| first_indexed | 2024-12-19T02:47:15Z |
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| institution | Directory Open Access Journal |
| issn | 1471-2172 |
| language | English |
| last_indexed | 2024-12-19T02:47:15Z |
| publishDate | 2012-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Immunology |
| spelling | doaj.art-3c5dd24ed71846a5b904c8b4cc46c40c2022-12-21T20:38:49ZengBMCBMC Immunology1471-21722012-12-011317210.1186/1471-2172-13-72Human CD72 splicing isoform responsible for resistance to systemic lupus erythematosus regulates serum immunoglobulin level and is localized in endoplasmic reticulumHitomi YukiAdachi TakahiroTsuchiya NaoyukiHonda Zen-IchiroTokunaga KatsushiTsubata Takeshi<p>Abstract</p> <p>Background</p> <p>CD72 is an inhibitory co-receptor expressed on B cells. We previously demonstrated significant association of the polymorphism of the <it>CD72</it> gene with susceptibility to human systemic lupus erythematosus (SLE) in individuals carrying a SLE-susceptible <it>FCGR2B</it> genotype (<it>FCGR2B-232Thr/Thr</it>). The human <it>CD72</it> locus generates a splicing isoform that lacks exon 8 (CD72Δex8) as well as full-length CD72 (CD72fl), and the <it>CD72</it> polymorphism regulates exon 8 skipping.</p> <p>Results</p> <p>Here we demonstrated that individuals carrying the disease-protective <it>CD72</it> genotype exhibit significantly lower serum immunoglobulin levels than do individuals carrying other <it>CD72</it> genotypes (<it>P</it> < 0.05). Although expression level of CD72fl in the peripheral blood B cells was similar regardless of <it>CD72</it> genotype, the protein level of CD72Δex8 was increased in individuals carrying the disease-protective <it>CD72</it> 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.</p> <p>Conclusion</p> <p>Human <it>CD72</it> polymorphism appears to regulate antibody production as well as susceptibility to SLE by regulating expression of ER-localizing CD72Δex8.</p>http://www.biomedcentral.com/1471-2172/13/72PolymorphismExon skippingC-type lectin domain |
| spellingShingle | Hitomi Yuki Adachi Takahiro Tsuchiya Naoyuki Honda Zen-Ichiro Tokunaga Katsushi Tsubata Takeshi Human CD72 splicing isoform responsible for resistance to systemic lupus erythematosus regulates serum immunoglobulin level and is localized in endoplasmic reticulum BMC Immunology Polymorphism Exon skipping C-type lectin domain |
| title | Human CD72 splicing isoform responsible for resistance to systemic lupus erythematosus regulates serum immunoglobulin level and is localized in endoplasmic reticulum |
| title_full | Human CD72 splicing isoform responsible for resistance to systemic lupus erythematosus regulates serum immunoglobulin level and is localized in endoplasmic reticulum |
| title_fullStr | Human CD72 splicing isoform responsible for resistance to systemic lupus erythematosus regulates serum immunoglobulin level and is localized in endoplasmic reticulum |
| title_full_unstemmed | Human CD72 splicing isoform responsible for resistance to systemic lupus erythematosus regulates serum immunoglobulin level and is localized in endoplasmic reticulum |
| title_short | Human CD72 splicing isoform responsible for resistance to systemic lupus erythematosus regulates serum immunoglobulin level and is localized in endoplasmic reticulum |
| title_sort | human cd72 splicing isoform responsible for resistance to systemic lupus erythematosus regulates serum immunoglobulin level and is localized in endoplasmic reticulum |
| topic | Polymorphism Exon skipping C-type lectin domain |
| url | http://www.biomedcentral.com/1471-2172/13/72 |
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