Analysis of the V_KI Family: Germline Genes from an SLE Patient and Expressed Autoantibodies

Abstract

Our studies of anti-DNA antibodies in systemic lupus erythematosus have demonstrated a preferential use of the V_KI family to encode light chains of antibodies that express the anti-DNA associated 31 idiotype. This idiotype is present on a high percentage of anti-DNA antibodies in approximately 80% of SLE patients^1,2. In this study, we employed PCR to obtain V_KI germline genes from a lupus patient in order to address the following questions: Do the V_KI germline genes of an individual with autoimmune disease differ from those of healthy individuals? What V_KI genes are used to encode autoantibodies and are they used to encode protective antibodies also? Does the V_KI 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_K genes are ordinarily derived from the J_K proximal region of the V_K locus, V_KI genes encoding autoantibodies derive primarily from the J_K distal region. It is not yet clear if this applies equally to V_KI encoded antibodies directed to foreign antigen.

Key Words:

• germline genes
• kappa chain
• somatic mutation
• systemic lupus erythematosus
• autoantibodies