Human monoclonal striational autoantibodies isolated from thymic B lymphocytes of patients with myasthenia gravis use V_H and V_L gene segments associated with the autoimmune repertoire

The production of autoantibodies reactive with components of skeletal muscle is characteristic of myasthenia gravis (MG) and is strongly associated with the presence of thymic epithelial tumors in patients with MG. The nucleotide sequences of the heavy and light chain variable regions (V_H and V_L) of three human monoclonal striated muscle antibodies (StrAb) isolated from thymic B lymphocyte lines from two patients with MG and thymoma were analyzed. The V_H and V_L gene segments used by these anti‐striated muscle antibodies appear to be derived from the same repertoire of gene segments as have been found in other autoantibodies isolated from patients with a number of different autoimmune diseases. While the IgM StrAb SA‐1A is a direct copy of germ‐line V_H and V_L gene segments, analysis of the IgG StrAb SA‐4A and SA‐4B, which may be more representative of antibodies found in the serum of MG patients, suggests that the processes of antigenic selection and somatic mutation may contribute to the generation of autoantibodies in MG.