Primary structure of the antigen-binding domains of a human oligodendrocyte-reactive IgM monoclonal antibody derived from a patient with multiple sclerosis.

Several murine IgM monoclonal antibodies (mAbs) promoting remyelination in mice were shown to be germline gene-encoded natural autoantibodies that react with oligodendrocytes and intracellular antigens. Here, we show that human oligodendrocyte-reactive IgM mAb DS1F8 derived from a patient with multiple sclerosis targets microtubule-like structures similar to the murine mAbs. Sequencing of the cDNAs of the variable regions revealed that the antigen-binding domains are also encoded by germline genes. These similarities of mAb DS1F8 to the murine mAbs promoting remyelination suggest that this human mAb is a natural autoantibody. This may imply that the engineering of human autoantibodies for therapy of demyelinating diseases is feasible.