The long term objective of this project is to define relationships between mechanisms that somatically alter immunoglobulin germ line variable (V) region sequences and the production of autoantibody specificities and autoimmune diseases. The immediate major goal of this work is to determine whether V region germ line sequence somatic variants can be associated with autoantibody production and murine systemic lupus erythematosus. Somatic V region variants of the single germ line lambda 1 light chain V region sequence will be detected by isoelectric focusing (IEF) and serologically in RIA systems. An association of V region somatic variants with autoimmune disease will be evaluated by the presence, proportion and IEF spectrotype of lambda 1 V region somatic sequence variants in lambda bearing serum autoantibody, antibody, and hybridomas from SLE-prone mice with spontaneous and lipid A induced early life fatal glomerulonephritis, from mice with lipid A induced low-grade glomerulonephritis, and from normal counterpart controls. Lambda V1 sequence variants found in hybridomas with autoantibody specificity will be examined for their abilities to contribute to the binding site of immunoglobulin heavy chain-lambda 1 recombinant antibody molecules.
