Nonrandom X chromosome inactivation in natural killer cells from obligate carriers of X-linked severe combined immunodeficiency.
X-linked severe combined immunodeficiency (XSCID) is characterized by hypogammaglobulinemia, markedly reduced numbers of T cells, absent mitogen responses, decreased numbers of NK cells, and normal or elevated numbers of B cells. The abnormalities in the NK cell and B cell lineages could be attributed to dependence of these cell lineages on T cells or T cell-derived factors, or to expression of the XSCID gene defect in these cell lineages. In past experiments, we have examined X chromosome inactivation patterns in T cells and cultured B cells from female obligate carriers of XSCID and have found that both cell lineages demonstrate nonrandom X chromosome inactivation. This indicates that the gene defect is intrinsic to both of these cell lineages. In the present experiments, a polymerase chain reaction technique was used to evaluate X chromosome inactivation patterns in highly purified populations of freshly isolated NK cells, B cells, CD4+ cells, and CD8+ cells from three obligate carriers of XSCID. All four lymphoid cell populations from these three women exhibited exclusive use of a single X as the active X. In contrast, both X chromosomes were used as the active X in neutrophils and monocytes. These findings indicate that the XSCID gene is expressed in the NK cell lineage as well as in T cells and B cells. This observation makes it highly unlikely that the XSCID gene is involved in Ag receptor gene rearrangements.
Wengler
G S
GS
Department of Pediatrics, University of Tennessee, Memphis.
Allen
R C
RC
Parolini
O
O
Smith
H
H
Conley
M E
ME
D001402:B-Lymphocytes / Q000648:ultrastructure; D015496:CD4-Positive T-Lymphocytes / Q000648:ultrastructure; D005260:Female; D008040:Genetic Linkage; D006579:Heterozygote; D006801:Humans; D007694:Killer Cells, Natural / Q000648:ultrastructure*; D008297:Male; D016511:Severe Combined Immunodeficiency / Q000235:genetics*; D014960:X Chromosome