{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T05:20:10Z","timestamp":1740374410585,"version":"3.37.3"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[1995,1,1]],"date-time":"1995-01-01T00:00:00Z","timestamp":788918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,6,28]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:p>Patients with common variable immunodeficiency (CVID) display reduced levels of two or all three of the major immunoglobulin isotypes, and the deficiency is characterized by failure of B cells to differentiate into plasma cells in many cases. A patient (14 years old, female) showed normal serum IgM levels and low serum IgG and IgA levels, including low levels of all IgG subclasses. Northern blot analysis suggested that the patient's B cells may be defective at the immunoglobulin heavy chain isotype switch. The germ-line C\u03b31 transcript was amplified from cDNA of healthy controls by the addition of recombinant IL-2 (rIL-2) to pokeweed mitogen-stimulated peripheral mononuclear cells or Staphylococcus aureus Cowan I (SAC)-stimulated IgM-producing lymphoblastoid cell lines (LCL) transformed by Epstein-Barr virus, while it was not amplified from cDNA of the patient. In the I\u03b31 region of LCL cultured with SAC plus rIL-2, the inner cytosine in the 5\u2032C-C-G-G 3\u2032sequence nearest the 3\u2032site of the I\u03b31 region, at least, was not completely unmethylated in the patient. Moreover, the DNase I hypersensitive site was not induced in the patient's LCL by SAC plus rIL-2. These results indicate that the defects of the immunoglobulin heavy chain isotype switch in the patient's B cells are due to failure in the synthesis of germ-line C\u03b3 transcripts, and this may be caused by defects in opening of the chromatin structures of specific switch regions.<\/jats:p>","DOI":"10.1111\/j.1365-2249.1995.tb03467.x","type":"journal-article","created":{"date-parts":[[2010,7,26]],"date-time":"2010-07-26T23:10:09Z","timestamp":1280185809000},"page":"21-28","source":"Crossref","is-referenced-by-count":2,"title":["Failure of IgG production due to a defect in the opening of the chromatin structure of I\u03b31 region in a patient with IgG and IgA deficiency"],"prefix":"10.1093","volume":"99","author":[{"given":"N","family":"Kondo","sequence":"first","affiliation":[{"name":"Department of Paediatrics, Gifu University School of Medicine, Tsukasa-machi, Gifu, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Gifu University School of Medicine, Tsukasa-machi, Gifu, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Kasahara","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Gifu University School of Medicine, Tsukasa-machi, Gifu, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Gifu University School of Medicine, Tsukasa-machi, Gifu, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Kameyama","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Gifu University School of Medicine, Tsukasa-machi, Gifu, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Orii","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Gifu University School of Medicine, Tsukasa-machi, Gifu, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2008,6,28]]},"reference":[{"key":"2022011517425602200_b1","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/302575a0","article-title":"Somatic generation of antibody diversity","volume":"302","author":"Tonegawa","year":"1983","journal-title":"Nature"},{"key":"2022011517425602200_b2","doi-asserted-by":"crossref","first-page":"7704","DOI":"10.1073\/pnas.85.20.7704","article-title":"Immunoglobulin heavy-chain switching may be directed by prior induction of transcripts from constant-region genes","volume":"85","author":"Stavnezer","year":"1988","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022011517425602200_b3","doi-asserted-by":"crossref","first-page":"2829","DOI":"10.1073\/pnas.86.8.2829","article-title":"Synthesis of germ-line \u03b31 immunoglobulin heavy-chain transcripts in resting B cells: induction by interleukin 4 and inhibition by interferon \u03b3","volume":"86","author":"Berton","year":"1989","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022011517425602200_b4","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1084\/jem.172.2.463","article-title":"Structure and expression of germline \u03b5 transcripts in human B cells induced by interleukin 4 to switch to IgE production","volume":"172","author":"Gauchat","year":"1990","journal-title":"J Exp Med"},{"key":"2022011517425602200_b5","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1093\/intimm\/1.6.631","article-title":"Production of sterile transcripts of C\u03b3 genes in an IgM-producing human neoplastic B cell line that switches to IgG-producing cells","volume":"1","author":"Sideras","year":"1989","journal-title":"Int Immunol"},{"key":"2022011517425602200_b6","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1093\/intimm\/1.6.570","article-title":"An interleukin 4-induced DNase I hypersensitive site indicates opening of the \u03b31 switch region prior to switch recombination","volume":"1","author":"Schmitz","year":"1989","journal-title":"Int Immunol"},{"key":"2022011517425602200_b7","doi-asserted-by":"crossref","first-page":"3478","DOI":"10.4049\/jimmunol.151.7.3478","article-title":"Regulation of C\u03b3 subclass germ-line transcripts in human peripheral blood B cells","volume":"151","author":"Kitani","year":"1993","journal-title":"J Immunol"},{"key":"2022011517425602200_b8","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1056\/NEJM196609292751307","article-title":"The gamma globulins. 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