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PMID: 1512540 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Journal of experimental medicine ·Vol. 176 ·No. 3 ·1992-09-01 ·Pages 761-79

Tillman DM, Jou NT, Hill RJ, Marion TN

Abstract

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.

MeSH Terms
Amino Acid Sequence Animals Antibodies, Antinuclear/immunology Arginine/chemistry B-Lymphocytes/cytology,immunology Clone Cells DNA/immunology DNA, Recombinant Hybridomas Immunoglobulin G/immunology Immunoglobulin Heavy Chains/genetics,immunology Immunoglobulin M/immunology Immunoglobulin Variable Region/genetics,immunology Mice Mice, Inbred NZB Molecular Sequence Data Sequence Alignment
Chemicals
Antibodies, Antinuclear DNA, Recombinant Immunoglobulin G Immunoglobulin Heavy Chains Immunoglobulin M Immunoglobulin Variable Region DNA Arginine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Tillman D M
Department of Microbiology and Immunology, University of Tennessee, Memphis 38163.
Jou N T
Hill R J
Marion T N
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.176.3.761
Published
1992-09-01
Pages
761-79
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2119342
Subset
IM
Grants
NIAID NIH HHS · AI-26833 · United States
Databases
GENBANK
L14731, L14732, L14733, L14734, L14735, L14736, L14737, L14738, L14739, L14740
External Links
PubMed source DOI: 10.1084/jem.176.3.761 PMC Full Text View journal details
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