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 journalArticlepeer-review

30 Scopus citations

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 - Jul 1995
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Pathology and Forensic Medicine
  • Immunology

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