Analysis of the V kappa I family: germline genes from an SLE patient and expressed autoantibodies.
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.
Manheimer-Lory
A
A
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Monhian
R
R
Splaver
A
A
Gaynor
B
B
Diamond
B
B
D001323:Autoantibodies / Q000235:genetics*; D001483:Base Sequence; D005803:Genes, Immunoglobulin; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data
D001323:Autoantibodies; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains