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.

journal_name

Clin Exp Immunol

authors

Goodship J,Malcolm S,Levinsky RJ

doi

10.1111/j.1365-2249.1991.tb05579.x

subject

Has Abstract

pub_date

1991-01-01 00:00:00

pages

4-9

issue

1

eissn

0009-9104

issn

1365-2249

journal_volume

83

pub_type

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