SOMATIC MUTATION IN AUTOANTIBODY-ASSOCIATED V-H GENES OF CIRCULATING IGM(-CELLS()IGD(+) B)

Naive B cells expressing IgM and IgD on their surface have no or littl e somatic mutations in V genes. We have demonstrated that the human Ig M(+)IgD(+)B cell clone (0-81), which expresses nephritogenic idiotypes , produces IgM anti-DNA antibodies which show monospecificity to DNA. Using a DNA probe which specifically links to the V, gene of antibody 0-81, we identified the counterpart germ-line V gene of 0-81, V3-7, wh ich appears to be used by pathogenic autoantibodies in humans. Clone 0 -81, which may belong to naive B cells in terms of cell phenotype, use s a somatically mutated V3-7 gene. We further studied DNA sequences of V3-7 genes in circulating IgM(+)IgD(+)B cells from normal subjects an d patients with systemic lupus erythematosus (SLE). The results reveal ed that rearranged V3-7 genes in IgM(+)IgD(+)B cells from patients wit h SLE contained somatically mutated sequences at significantly increas ed frequencies. These data indicate an abnormal maturation of B cells in autoimmune states that may be associated with an escape of self-rea ctive B cells from the elimination process in the germinal center.