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Related Experiment Videos

VH and VL gene elements that encode human antibodies to DNA

S Hoch1, J Schwaber

  • 1Department of Pediatrics, Medical College of Pennsylvania, Hahnemann University, Philadelphia 19102, USA.

Clinical Immunology and Immunopathology
|July 1, 1996
PubMed
Summary

Researchers sequenced DNA-binding antibodies, finding common variable heavy (VH) gene elements in low-affinity antibodies. This suggests DNA may not be the primary driver for high-affinity antibody development.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Antibodies against DNA are crucial in autoimmune diseases.
  • Previous research suggested antigen-driven affinity maturation for high-affinity anti-DNA antibodies.

Purpose of the Study:

  • To determine the cDNA sequence of variable regions of heavy and light chains of low-affinity DNA-binding antibodies.
  • To investigate the genetic basis of antibody reactivity to DNA.

Main Methods:

  • cDNA sequencing of antibody variable heavy and light chains.
  • Analysis of Variable Heavy (VH) and Variable Light (VL) gene element utilization.
  • Comparison of gene usage in low-affinity versus high-affinity anti-DNA antibodies.

Main Results:

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  • Identified specific VH gene elements (VH26, VH1.9III) in low-affinity anti-DNA antibodies, associated with novel D gene-encoded CDR3s.
  • Discovered previously unidentified VL gene elements in these antibodies.
  • Found that only a subset of high-affinity anti-DNA antibodies utilize these low-affinity VH genes.

Conclusions:

  • The limited repertoire of VH genes in low-affinity anti-DNA antibodies suggests most relevant VH gene elements have been identified.
  • The data indicates that DNA is unlikely to be the sole driving antigen for high-affinity antibody development, challenging previous assumptions.