The double edged sword of the immune response

Mutational analysis of a murine anti-pneumococcal, anti-DNA antibody

Chaim Putterman, Wacharee Limpanasithikul, Morris Edelman, Betty Diamond

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Anti-double-stranded (ds) DNA antibodies are not only an important diagnostic marker for SLE, but also play an important role in tissue injury. Microbial antigen may be a stimulus for the production of these antibodies. We isolated 99D.7E, an IgG2b monoclonal antibody from a nonautoimmune BALB/c mouse that is cross-reactive with both ds-DNA and phosphorylcholine, the dominant hapten on the pneumococcal cell wall. While partially protective against a bacterial challenge, 99D.7E is also pathogenic to the kidney. To identify those molecular motifs that confer on anti-PC antibodies the potential for autoreactivity, we created a panel of 99D.7E mutants with single amino acid substitutions in the heavy chain, and examined the changes in antigen binding and renal deposition. Our results support the hypothesis that charge and affinity for dsDNA are not adequate predictors of the pathogenicity of anti-DNA antibodies. Differential renal damage from anti-dsDNA antibodies may be due to differences in fine specificity, rather than differential affinity for dsDNA. Importantly, high affinity IgG antibodies cross-reactive with bacterial and self antigen exist and can display pathogenic potential, suggesting that defects in peripheral regulation of B cells, activated by foreign antigen but cross-reactive with self antigen, might lead to autoimmune disorders.

Original languageEnglish (US)
Pages (from-to)2251-2259
Number of pages9
JournalJournal of Clinical Investigation
Volume97
Issue number10
StatePublished - May 15 1996

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Antinuclear Antibodies
Autoantigens
Kidney
Antigens
Anti-Idiotypic Antibodies
Bacterial Antigens
Antibody Affinity
Phosphorylcholine
Haptens
DNA
Amino Acid Substitution
Cell Wall
Antibody Formation
Virulence
B-Lymphocytes
Immunoglobulin G
Monoclonal Antibodies
Antibodies
Wounds and Injuries

Keywords

  • Anti-DNA antibodies
  • Antibacterial antibodies
  • Cross-reactivity
  • Pathogenicity
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Medicine(all)

Cite this

The double edged sword of the immune response : Mutational analysis of a murine anti-pneumococcal, anti-DNA antibody. / Putterman, Chaim; Limpanasithikul, Wacharee; Edelman, Morris; Diamond, Betty.

In: Journal of Clinical Investigation, Vol. 97, No. 10, 15.05.1996, p. 2251-2259.

Research output: Contribution to journalArticle

Putterman, Chaim ; Limpanasithikul, Wacharee ; Edelman, Morris ; Diamond, Betty. / The double edged sword of the immune response : Mutational analysis of a murine anti-pneumococcal, anti-DNA antibody. In: Journal of Clinical Investigation. 1996 ; Vol. 97, No. 10. pp. 2251-2259.
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