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

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Abstract
Our studies of anti-DNA antibodies in systemic lupus erythematosus have demonstrated a preferential use of the VKI 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 patients1,2. In this study, we employed PCR to obtain VKI germline genes from a lupus patient in order to address the following questions: Do the VKI germline genes of an individual with autoimmune disease differ from those of healthy individuals? What VKI genes are used to encode autoantibodies and are they used to encode protective antibodies also? Does the VKI 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 VK genes are ordinarily derived from the JK proximal region of the VK locus, VKI genes encoding autoantibodies derive primarily from the JK distal region. It is not yet clear if this applies equally to VKI encoded antibodies directed to foreign antigen.