Immunoglobulin gene expression in xid mice: Defective expression of secreted and membrane α-heavy chain RNA

CNA/N mice bearing the X-linked immunodeficiency (xid) gene(s) demonstrate overall decreased numbers of B-cells, impaired immune responses to TI-2 antigens and decreased serum IgM, IgG3 and to a lesser extent IgG1 and IgA. In these experiments we examined equal numbers of B-cells (cells capable of regeneration of surface Ig) from PP, MLN and spleens of xid and control mice for immunoglobulin gene expression. B-cells present in CBA/N mice exhibit control levels of Ig isotypespecific mRNA accumulation and transcription. Oligonucleotide probes directed against membrane and secreted exons of β, γ and α genes were synthesized and hybridized to B-cell RNA from CBA/N and CBA/J mice to determine relative levels of each isotype- and exon-specific mRNA. Results revealed decreased α_sRNA:α_mRNA in splenic B-cells of xid mice when compared to control animals. Northern blot analysis of total tissue polysomal RNA demonstrated enhanced expression of the (larger) membrane form of α-mRNA (α_m-RNA) of CBA/N when compared to CBA/J mice. This was especially apparent in splenic preparations; these and other studies have shown that both control and xid PP and MLN express enhanced levels of the membrane forms of each Ig heavy chain isotype RNA when compared to splenic RNA levels. These data suggest the presence of a defective regulation of membrane and secreted α in B-cell subpopulations of xid mice.