Both IgM and IgG anti-DNA antibodies are the products of clonally selective B cell stimulation in (NZB x NZW)F1 mice

J Exp Med. 1992 Sep 1;176(3):761-79. doi: 10.1084/jem.176.3.761.


Disease activity in systemic lupus erythematosus is closely associated with the appearance of immunoglobulin (Ig)G antibody to native DNA in both humans and mice. Like normal antibody responses, the anti-DNA autoantibody first appears as IgM and then switches to IgG. Structural studies of IgG anti-DNA suggest that these antibodies are the products of clonally selected, specifically stimulated B cells. The origins of the IgM anti-DNA have been less clear. To determine whether the earlier appearing IgM anti-DNA antibody in autoimmune mice also derives from clonally selected, specifically stimulated B cells or B cells activated by nonselective, polyclonal stimuli, we have analyzed the molecular and serological characteristics of a large number of monoclonal IgM anti-DNA antibodies from autoimmune (NZB x NZW)F1 mice. We have also analyzed IgM and IgG anti-DNA hybridomas obtained from the same individual mice to determine how the later-appearing IgG autoantibody may be related to the earlier-appearing IgM autoantibody within an individual mouse. The results demonstrate that: (a) IgM anti-DNA, like IgG, has the characteristics of a specifically stimulated antibody; (b) IgM and IgG anti-DNA antibodies have similar variable region structures and within individual mice may be produced by B cells derived from the same clonal precursors; (c) recurrent germline and somatically derived VH and VL structures may influence the specificity of anti-DNA monoclonal antibody for denatured vs. native DNA; and (d) the results provide a structural explanation for the selective development of IgG antibody to native DNA as autoimmunity to DNA progresses in (NZB x NZW)F1 mice.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Antinuclear / immunology*
  • Arginine / chemistry
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • Clone Cells
  • DNA / immunology*
  • DNA, Recombinant
  • Hybridomas
  • Immunoglobulin G / immunology*
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Heavy Chains / immunology
  • Immunoglobulin M / immunology*
  • Immunoglobulin Variable Region / genetics
  • Immunoglobulin Variable Region / immunology
  • Mice
  • Mice, Inbred NZB
  • Molecular Sequence Data
  • Sequence Alignment


  • Antibodies, Antinuclear
  • DNA, Recombinant
  • Immunoglobulin G
  • Immunoglobulin Heavy Chains
  • Immunoglobulin M
  • Immunoglobulin Variable Region
  • DNA
  • Arginine

Associated data

  • GENBANK/L14731
  • GENBANK/L14732
  • GENBANK/L14733
  • GENBANK/L14734
  • GENBANK/L14735
  • GENBANK/L14736
  • GENBANK/L14737
  • GENBANK/L14738
  • GENBANK/L14739
  • GENBANK/L14740