A monoclonal autoantibody which promotes central nervous system remyelination is highly polyreactive to multiple known and novel antigens

Abstract

A monoclonal antibody (mAb), designated SCH94.03, which promotes central nervous system remyelination in susceptible mice infected with Theiler's virus, has been proposed to be a natural autoantibody based on its germline immunoglobulin sequence. To identify the potential antigens recognized by mAb SCH94.03, a rat brain λgt11 cDNA expression library was screened with this antibody. Nine independent clones were identified. Five clones were identical or highly similar to known cDNAs or proteins (rat kinesin light chain, mouse thrombospondin 1, mouse oncofetal antigen, RNA polymerase beta subunit and nuclear phosphoprotein). Four clones, designated REM#1, REM#2, REM#3 and REM#4, contained open reading frames, but were not homologous to any known genes or proteins. The reactivity of SCH94.03 with all nine clones was specific in that all nine clones identified contained continuous open reading frames and none of nine control IgM mAbs showed reactivity with any of the nine cDNA clones. The precise specificity of binding of mAb SCH94.03 was demonstrated by the absence of reactivity to the identified clones with IgM Ab from B cell lymphoma (CH12) which has identical cDNA sequences with mAb SCH94.03, but differ only in the heavy chain CDR3 N region. Our studies support the hypothesis that highly polyreactive natural autoantibodies can play a role in promoting central nervous system remyelination.