Elsevier

Molecular Immunology

Volume 24, Issue 9, September 1987, Pages 995-1004
Molecular Immunology

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

https://doi.org/10.1016/0161-5890(87)90012-5Get rights and content

Abstract

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 αsRNA:αmRNA 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 (αm-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.

References (44)

  • B.A. White et al.

    Cytoplasmic dot hybridization. Simple analysis of relative mRNA levels in multiple small cell or tissue samples

    J. biol. Chem.

    (1982)
  • G.E. Woloschak

    Comparison of immunoglobulin heavy chain isotype expression in Peyer's patch and splenic B-cells

    Molec. Immun.

    (1986)
  • J.M. Adams et al.

    Molecular cloning of mouse immunoglobulin heavy chain messenger ribonucleic acids coding for μ, γ 1, γ2a, and γ3 chains

    Biochemistry

    (1980)
  • S.H. Clarke et al.

    Amino acid sequence of a phosphocholinebinding antibody from an immune defective CBA/N mouse employing the T15 VH region associated with unusual DH, JH and VK segments

    J. Immun.

    (1984)
  • E.R. Clough et al.

    CBA/N × BALB/c F1 male and female mice can be primed to express quantitatively equivalent secondary anti-phosphocholine responses

    J. Immun.

    (1981)
  • J.H. Eldridge et al.

    Evidence for a mature B cell subpopulation in Peyer's patches of young adult xid mice

    J. exp. Med.

    (1983)
  • J.H. Eldridge et al.

    Expression of Lyb-5 and M1s determinants by Peyer's patch B lymphocytes of X-linked immunodeficient mice

    J. Immun.

    (1984)
  • J.M. Fidler et al.

    B lymphocyte differentiation in the CBA/N mouse: a delay in maturation rather than a total arrest

    J. Immun.

    (1980)
  • T. Gurney et al.

    Daba-fluorescence assay for submicrogram amounts of DNA

  • K.W. Hunter et al.

    Defective resistance to Plasmodium yoelli in CBA/N mice

    J. Immun.

    (1979)
  • J.J. Kenny et al.

    Contribution of Lyb-5 + and Lyb-5− B-cells to the primary and secondary phosphocholine-specific antibody response

    J. Immun.

    (1983)
  • H. Kikutani et al.

    Effect of B cell differentiation factor (BCDF) on biosynthesis and secretion of immunoglobulin molecules in human B cell lines

    J. Immun.

    (1985)

    • Cited by (0)

    ☆

    This work was supported in part by American Cancer Society Grant No. IM-348 and by the Mayo Foundation.

    View full text
    Copyright © 1987 Published by Elsevier Ltd.