title: Evidence that X-linked severe combined immunodeficiency is not a differentiation defect of T lymphocytes.
abstract: In order to gain information about the nature of the defect in X-linked severe combined immunodeficiency (XSCID), we investigated gene expression in different lymphoid and haematopoietic cells of female carriers by looking for non-random X chromosome usage. We have shown non-random X chromosome usage in T lymphocyte enriched (E+) fraction in all carriers. E- cells and monocytes showed non-random X chromosome usage in three carriers tested. In the B cell series one carrier showed non-random inactivation in all EBV lines tested (10) and the same X chromosome was shown to be active in all cells. In other carriers there was a preference for use of the normal X chromosome but some B cell lines used the mutant X as well as the normal X. Similar results were found with granulocytes. In two female carriers DNA made directly from whole blood showed a non-random pattern of X chromosome usage. In fibroblast cultures from two female carriers more cells had the normal gene on the active X chromosome than had the defective gene on the active X chromosome. Within families there was heterogeneous expression of the gene. The gene that is defective in XSCID is expressed in all the cell types studied and, therefore, is not a T lymphocyte differentiation gene. The results are consistent with the gene being in a metabolic pathway as in certain autosomal recessive forms of SCID i.e. adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency.
authors.affiliation: Department of Immunology, Institute of Child Health, London, England.
authors.forename: J
authors.initials: J
authors.lastname: Goodship
authors.forename: S
authors.initials: S
authors.lastname: Malcolm
authors.forename: R J
authors.initials: RJ
authors.lastname: Levinsky
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation; D004247:DNA / Q000032:analysis; D004303:Dosage Compensation, Genetic; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D008040:Genetic Linkage; D006098:Granulocytes / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D014960:X Chromosome
chemical_list: D004247:DNA