Analysis of the V kappa I family: germline genes from an SLE patient and expressed autoantibodies

Autoimmunity. 1995;20(4):259-65. doi: 10.3109/08916939508995703.

Abstract

Our studies of anti-DNA antibodies in systemic lupus erythematosus have demonstrated a preferential use of the V kappa I family to encode light chains of antibodies that express the anti-DNA associated 3I idiotype. This idiotype is present on a high percentage of anti-DNA antibodies in approximately 80% of SLE patients1,2. In this study, we employed PCR to obtain V kappa I germline genes from a lupus patient in order to address the following questions: Do the V kappa I germline genes of an individual with autoimmune disease differ from those of healthy individuals? What V kappa I genes are used to encode autoantibodies and are they used to encode protective antibodies also? Does the V kappa I gene family display peculiarities in V gene segment rearrangement or somatic mutation? Our analysis shows that the coding region sequences of germline genes of an autoimmune individual are highly homologous to those of non-autoimmune individuals. In addition, the same germline genes can be utilized to encode antibodies to both exogenous and self antigens. While rearranged V kappa genes are ordinarily derived from the J kappa proximal region of the V kappa locus, V kappa I genes encoding autoantibodies derive primarily from the J kappa distal region. It is not yet clear if this applies equally to V kappa I encoded antibodies directed to foreign antigen.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Autoantibodies / genetics*
  • Base Sequence
  • Genes, Immunoglobulin*
  • Humans
  • Immunoglobulin Variable Region / genetics*
  • Immunoglobulin kappa-Chains / genetics*
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / immunology
  • Molecular Sequence Data

Substances

  • Autoantibodies
  • Immunoglobulin Variable Region
  • Immunoglobulin kappa-Chains

Associated data

  • GENBANK/UNKNOWN