Coalescence of B cell receptor and invariant chain MHC II in a raft‐like membrane domain

[摘要] TheBCRbindsantigenforprocessingandsubsequentpresentationonMHCIImolecules.PolyvalentantigeninducesBCRclusteringandtargetingtoendocyticprocessingcompartments,whicharealsoaccessedbyIi‐MHCII.Here,wereportthatclusteredBCRisabletoteamupwithIi‐MHCIIalreadyattheplasmamembraneofmouseB‐lymphocytes.ColocalizationofBCRandIi‐MHCIIonthecellsurfacerequiredclusteringofbothtypesofmolecules.Theclusteringofonlyonetypedidnottriggertherecruitmentoftheother.Ii‐boundMIF(aligandofIi)alsocolocalizedwithclusteredBCRuponoligomerizationofMIFonthesurfaceoftheBcell.Abundantsurfacemolecules,suchasB220orTfnR,didnotcoclusterwiththeBCR.Somemembraneraft‐associatedmolecules,suchaspeptide‐loadedMHCII,coclusteredwiththeBCR,whereasothers,suchasGM1,didnot.TheformationofaBCR‐andIi‐MHCII‐containingmembranedomainbyantibody‐mediatedclusteringwasindependentofF‐actinandledtothecoendocytosisofitsconstituents.WitharapidBrij98extractionmethod,itwaspossibletocapturethismembranedomainbiochemicallyasaDRM.IiandclusteredBCRwerepresentonthesameDRM,asshownbyimmunoisolation.ThecoalescenceofBCRandIi‐MHCIIincreasedtyrosinephosphorylation,indicativeofenhancedBCRsignaling.OurworksuggestsanovelroleforMIFandIi‐MHCIIinBCR‐mediatedantigenprocessing...

[学科分类] 生理学

[关键词] antigen presentation;B‐lymphocyte;BCR;CD74;MIF;lipid raft