The Influence of Variable-Region Somatic Mutations on the Specificity and Pathogenicity of Murine Monoclonal Anti-DNA Antibodies

Gary S. Gilkeson, Keith Bernstein, Anne M.M. Pippen, Stephen H. Clarke, Tony Marion, David S. Pisetsky, Philip Ruiz, James B. Lefkowith

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Antibodies to DNA (anti-DNA) occur prominently in systemic lupus erythematosus and provoke inflammatory damage in the kidneys. To determine the factors that confer pathogenicity on antibodies of this specificity, we investigated the in vitro and in vivo glomerular binding by members of four clonally related sets of monoclonal anti-DNA antibodies from lupus mice. Somatic mutations within the clonal sets enhanced binding to double-stranded DNA (dsDNA). Binding to permeabilized glomeruli in vitro was observed among affinity-purified preparations of these antibodies independent of specificity for dsDNA. In normal mice injected with hybridoma cell lines, nephritis as assessed by histology and immunofluorescence did not correlate with antibody affinity for DNA. By multivariate analysis, in vitro glomerular binding was the most predictive parameter of histologic outcome. These findings indicate that somatic mutations occurring during maturation of the autoimmune response do not necessarily enhance pathogenicity.

Original languageEnglish (US)
Pages (from-to)59-67
Number of pages9
JournalClinical Immunology and Immunopathology
Volume76
Issue number1
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

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Virulence
Anti-Idiotypic Antibodies
Antibody Specificity
Monoclonal Antibodies
Mutation
Antibody Affinity
Antibodies
Nephritis
DNA
Hybridomas
Virulence Factors
Autoimmunity
Systemic Lupus Erythematosus
Fluorescent Antibody Technique
Histology
Multivariate Analysis
Kidney
Cell Line
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Pathology and Forensic Medicine
  • Immunology

Cite this

The Influence of Variable-Region Somatic Mutations on the Specificity and Pathogenicity of Murine Monoclonal Anti-DNA Antibodies. / Gilkeson, Gary S.; Bernstein, Keith; Pippen, Anne M.M.; Clarke, Stephen H.; Marion, Tony; Pisetsky, David S.; Ruiz, Philip; Lefkowith, James B.

In: Clinical Immunology and Immunopathology, Vol. 76, No. 1, 01.01.1995, p. 59-67.

Research output: Contribution to journalArticle

Gilkeson, Gary S. ; Bernstein, Keith ; Pippen, Anne M.M. ; Clarke, Stephen H. ; Marion, Tony ; Pisetsky, David S. ; Ruiz, Philip ; Lefkowith, James B. / The Influence of Variable-Region Somatic Mutations on the Specificity and Pathogenicity of Murine Monoclonal Anti-DNA Antibodies. In: Clinical Immunology and Immunopathology. 1995 ; Vol. 76, No. 1. pp. 59-67.
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