A UNIQUE POPULATION OF CIRCULATING AUTOANTIBODIES PROMOTES CENTRAL-NERVOUS-SYSTEM REMYELINATION

In previous studies we demonstrated that the humoral immune response d irected against unique central nervous system (CNS) antigens enhanced CNS remyelination in the Theiler's virus experimental model of multipl e sclerosis (MS). To expend on this observation, a mouse IgM kappa mon oclonal antibody (mAb) which enhances CNS remyelination, was raised ag ainst normal mouse spinal cord homogenate. Characterization of this mA b revealed that it is polyreactive towards variety of intracellular an tigens but also reacts to an unidentified surface antigen on oligodend rocytes. The mAb is encoded by germline immunoglobulin genes without s omatic mutations consistent with the observation that it is a natural autoantibody. Recently we generated another mouse IgM kappa mAb raised against normal spinal cord homogenate, which also promotes CNS remyel ination. Further characterization revealed that both mAbs which promot e remyelination have similar binding characteristics. Conventionally A bs which recognize normal CNS components, especially oligodendrocytes or myelin, have been considered to be a disease marker or be involved in the pathogenesis of MS. However, we have identified a unique popula tion of circulating autoantibodies which ore beneficial for myelin rep air. Therefore this observation indicates the need to reevaluate autoa ntibody production against myelin components in CSF and blood as marke rs of disease activity versus repair in MS.