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The human<jats:italic>CD72<\/jats:italic>locus generates a splicing isoform that lacks exon 8 (CD72\u0394ex8) as well as full-length CD72 (CD72fl), and the<jats:italic>CD72<\/jats:italic>polymorphism regulates exon 8 skipping.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here we demonstrated that individuals carrying the disease-protective<jats:italic>CD72<\/jats:italic>genotype exhibit significantly lower serum immunoglobulin levels than do individuals carrying other<jats:italic>CD72<\/jats:italic>genotypes (<jats:italic>P<\/jats:italic>&lt; 0.05). Although expression level of CD72fl in the peripheral blood B cells was similar regardless of<jats:italic>CD72<\/jats:italic>genotype, the protein level of CD72\u0394ex8 was increased in individuals carrying the disease-protective<jats:italic>CD72<\/jats:italic>genotype, suggesting a crucial role of CD72\u0394ex8 in regulation of antibody production. By expressing these human CD72 isoforms in mouse cell lines, we further demonstrated that CD72\u0394ex8 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Human<jats:italic>CD72<\/jats:italic>polymorphism appears to regulate antibody production as well as susceptibility to SLE by regulating expression of ER-localizing CD72\u0394ex8.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1471-2172-13-72","type":"journal-article","created":{"date-parts":[[2012,12,26]],"date-time":"2012-12-26T17:14:15Z","timestamp":1356542055000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Human CD72 splicing isoform responsible for resistance to systemic lupus erythematosus regulates serum immunoglobulin level and is localized in endoplasmic reticulum"],"prefix":"10.1186","volume":"13","author":[{"given":"Yuki","family":"Hitomi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Adachi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoyuki","family":"Tsuchiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zen-Ichiro","family":"Honda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsushi","family":"Tokunaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Tsubata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2012,12,26]]},"reference":[{"key":"492_CR1","doi-asserted-by":"publisher","first-page":"1352","DOI":"10.1073\/pnas.86.4.1352","volume":"86","author":"E Nakayama","year":"1989","unstructured":"Nakayama E, von Hoegen I, Parnes JR: Sequence of the Lyb-2 B-cell differentiation antigen defines a gene superfamily of receptors with inverted membrane orientation. 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