Chondroitin sulfate activates B cells in vitro, expands CD138+ cells in vivo, and interferes with established humoral immune responses

摘要

Glycosaminoglycanshaveanti‐inflammatorypropertiesandinteractwithavarietyofsolubleandmembrane‐boundmolecules.LittleisknownabouttheireffectsonBcellsandhumoralimmuneresponses.WeshowthatCSbutnotdextranorotherglycosaminoglycansinducesapronouncedproliferationofBcellsinvitrocomparedwithTLR4orTLR9ligands.WiththeuseofinhibitorsandKOmice,wedemonstratethatthisproliferationismediatedbythetyrosinekinasesBTKandSykbutindependentofCD44.AntibodiesagainstIg‐αorIg‐βcompletelyblockCS‐inducedBcellproliferation.InjectionofCSinmicefor4–5daysexpandsBcellsinthespleenandresultsinamarkedincreaseofCD138+cellsinthespleenthatisdependentonBTKbutindependentofCD4+Tcells.Long‐termtreatmentwithCSfor14daysalsoincreasesCD138+cellsinthebonemarrow.WhenmicewereimmunizedwithAPCorcollagenandtreatedwithCSforupto14daysduringprimaryoraftersecondaryimmuneresponses,antigen‐specifichumoralimmuneresponsesandantigen‐specificCD138+plasmacellsinthebonemarrowwerereducedsignificantly.ThesedatashowthatCD138+cells,inducedbytreatmentwithCS,migrateintothebonemarrowandmaydisplaceotherantigen‐specificplasmacells.Overall,CSisabletointerferemarkedlywithprimaryandfullyestablishedhumoralimmuneresponsesinmice...