INFLUENCE ON X CHROMOSOME MOSAICISM Results X Chromosome Expression in Hematopoietic Cells

CBA/N mice have an x-linked immunodeficiency that is mainly expressed by poor antibody production to some T-independent antigens, called TI-2 antigens (1-4) and to a few T-dependent antigens (5-8). This functional defect is associated with a failure in development of a late-appearing B lymphocyte subset (9) that can be defined in normal animals by distinctive surface antigens such as Lyb-3 (10), Lyb-5 (11), and others (12-14). Because many TI-2 antigens induce IgG antibody largely of the IgG3 subclass (15, 16), a normally minor subclass of IgG, and because CBA/N mice are deficient in IgG3 production (17), we proposed that the Lyb-3 +, -5 ÷ B cell subpopulation may be responsible for the bulk of IgG3 production and that IgG3 subclass response to any antigen would be defective in CBA/N (16). This has been confirmed for both T-independent and T-dependent antigens (5, 6, 16). Antibodies of other isotypes are less regularly influenced by the immunodeficiency (5). The mutation in CBA/N mice, called xid, is linked to the x chromosome (1). Because of x chromosome inactivation, females heterozygous for xid will be mosaics, with some cells expressing the xid-bearing x chromosome, others not. Further, the recessive nature of the xid trait results in heterozygous females that are phenotypically normal (1). By examining x chromosome expression in the cells of these animals, it should be possible to determine whether the effect of xid on B cell development is direct or indirect. Direct effects, whereby the normal counterpart of the xid gene product(s) is expressed within the B cell and permits its development, would result in unbalanced x chromosome mosaicism among B lymphocytes from xid heterozygous females, because only B cells expressing the normal x chromosome could develop. Conversely, indirect effects, where the xid gene product(s) is expressed by non-B cells that subsequently influence B cell development or function, would result in balanced mosaicism among B lymphocytes. Here we examine x chromosome expression in xid heterozygous female mice using alloenzymes of phosphoglycerate kinase1 (PGK1)1 as x chromosome markers.