Expression of an X-linked gene family (XLR) in late-stage B cells and its alteration by the xid mutation

Abstract

One of the most extensively studied X-linked immunodeficiency disorder is the xid mutation of the mouse strain CBA/N (reviewed in ref. 1). This mutation may involve a maturational defect as xid animals are unable to raise antibodies to soluble polysaccharide antigens, a function normally attributed to late-stage B cells^2,3. Moreover, studies using monoclonal antibodies have defined a B-cell surface antigen (BLA-2 or 14G8) that is expressed on most or all immature B lymphocytes, but not on a subpopulation of mature splenic B lymphocytes^4,5; this late-stage, 14G8 antigen-negative splenic B-cell subpopulation is apparently absent from mice bearing the xid defect⁵. In the accompanying paper⁶ we describe the isolation of a cDNA clone recognizing a family of genes on the X chromosome, at least some of whose members are closely linked to the xid trait. We report here that this gene family, XLR, is transcribed in certain B- and T-cell lineage tumours, but not in macrophage tumours, or liver or kidney cells. We show that it is transcribed principally in late-stage, 14G8-negative B-cell tumours and plasmacytomas, but not in immature B-cell or pre-B-cell tumours. We are able to detect transcription in all of 12 plasmacytomas (secretory B-cell tumours) derived from mice with normal X chromosomes, but not in three plasmacytomas carrying the xid mutation. These data, combined with the restriction fragment length polymorphism analysis linking the XLR gene family to the xid mutation⁶, suggests that the xid defect occurs within a member of this gene family.