{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:39:40Z","timestamp":1781105980055,"version":"3.54.1"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"9","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1988,5]]},"abstract":"<jats:p>X chromosome-linked severe combined immunodeficiency (XSCID) is characterized by markedly reduced numbers of T cells, the absence of proliferative responses to mitogens, and hypogammaglobulinemia but normal or elevated numbers of B cells. To determine if the failure of the B cells to produce immunoglobulin might be due to expression of the XSCID gene defect in B-lineage cells as well as T cells, we analyzed patterns of X chromosome inactivation in B cells from nine obligate carriers of this disorder. A series of somatic cell hybrids that selectively retained the active X chromosome was produced from Epstein-Barr virus-stimulated B cells from each woman. To distinguish between the two X chromosomes, the hybrids from each woman were analyzed using an X-linked restriction fragment length polymorphism for which the woman in question was heterozygous. In all obligate carriers of XSCID, the B-cell hybrids demonstrated preferential use of a single X chromosome, the nonmutant X, as the active X. To determine if the small number of B-cell hybrids that contained the mutant X were derived from an immature subset of B cells, lymphocytes from three carriers were separated into surface IgM positive and surface IgM negative B cells prior to exposure to Epstein-Barr virus and production of B-cell hybrids. The results demonstrated normal random X chromosome inactivation in B-cell hybrids derived from the less mature surface IgM positive B cells. In contrast, the pattern of X chromosome inactivation in the surface IgM negative B cells, which had undergone further replication and differentiation, was significantly nonrandom in all three experiments [logarithm of odds (lod) score greater than 3.0]. These results suggest that the XSCID gene product has a direct effect on B cells as well as T cells and is required during B-cell maturation.<\/jats:p>","DOI":"10.1073\/pnas.85.9.3090","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T06:54:14Z","timestamp":1149058454000},"page":"3090-3094","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":82,"title":["Nonrandom X chromosome inactivation in B cells from carriers of X chromosome-linked severe combined immunodeficiency."],"prefix":"10.1073","volume":"85","author":[{"given":"M E","family":"Conley","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Children's Hospital of Philadelphia, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Lavoie","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children's Hospital of Philadelphia, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Briggs","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children's Hospital of Philadelphia, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children's Hospital of Philadelphia, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Guerra","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children's Hospital of Philadelphia, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J M","family":"Puck","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children's Hospital of Philadelphia, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1988,5]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.85.9.3090","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T12:38:51Z","timestamp":1649853531000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.85.9.3090"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1988,5]]},"references-count":0,"journal-issue":{"issue":"9","published-print":{"date-parts":[[1988,5]]}},"alternative-id":["10.1073\/pnas.85.9.3090"],"URL":"https:\/\/doi.org\/10.1073\/pnas.85.9.3090","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1988,5]]},"assertion":[{"value":"1988-05-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}