ANALYSIS OF THE V-KAPPA-I FAMILY - GERMLINE GENES FROM AN SLE PATIENTAND EXPRESSED AUTOANTIBODIES

Our studies of anti-DNA antibodies in systemic lupus erythematosus hav e demonstrated a preferential use of the VkI family to encode light ch ains of antibodies that express the anti-DNA associated 31 idiotype. T his idiotype is present on a high percentage of anti-DNA antibodies in approximately 80% of SLE patients(1,2). In this study, we employed PC R to obtain VkI germline genes from a lupus patient in order to addres s 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 enco de protective antibodies also? Does the VkI gene family display peculi arities in V gene segment rearrangement or somatic mutation? Our analy sis shows that the coding region sequences of germline genes of an aut oimmune individual are highly homologous to those of non-autoimmune in dividuals. In addition, the same germline genes can be utilized to enc ode 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, VkI genes encoding autoantibodies derive primarily from the J(k) distal region. It is not yet clear if this applies equally to VkI encoded antibodies directed to foreign antigen.