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1、第13章淋巴細(xì)胞成熟與抗原受體基因的表達(dá)LymphocyteMaturation&AntigenReceptorExpression免疫細(xì)胞（immunocytes）凡參與免疫應(yīng)答或與免疫應(yīng)答有關(guān)的細(xì)胞包括：淋巴細(xì)胞單核巨噬細(xì)胞抗原遞呈細(xì)胞粒細(xì)胞、肥大細(xì)胞、血小板等淋巴細(xì)胞T淋巴細(xì)胞B淋巴細(xì)胞NK細(xì)胞免疫活性細(xì)胞(immunocompetentcell，ICC)T、B細(xì)胞均有特異性抗原受體，接受抗原刺激后能發(fā)生活化、增殖和分化，產(chǎn)生特異性免疫應(yīng)答，故稱(chēng)免疫活性細(xì)胞第一節(jié)B細(xì)胞成熟過(guò)程Bcellmaturation骨髓內(nèi)成熟骨髓外成熟B細(xì)胞因在骨髓（bonemarrow）或禽類(lèi)法氏囊（bursa
2、ofFabricius）中分化成熟而得名，簡(jiǎn)稱(chēng)B細(xì)胞ThediscoveryofBcellimmunity1957-BruceGlick,OhioStateUniversityStudiesonthefunctionofthealymphoidorganinthecloacalregionofthechickenthebursaofFabriciusBursectomy–noapparenteffectNoneofthebursectomisedchickensmadeanti-SalmonellaantibodiesBursawastheorganwhereantibodyproducing
3、cellsdevelopedAntibodyproducingcellswerethereaftercalledBcellsTransferfoetallivercellsOriginofBcellsandorganofBcellmaturationNoMatureBcellsAfterbirth,developmentcontinuesinthebonemarrowNormalbonemarrowDefectivebonemarrowMatureBcellsinperipheryBcelldevelopmentstartsinthefoetalliver起源：胎兒期—胎肝和骨髓出生后—骨髓兩
4、階段:骨髓內(nèi)成熟(抗原非依賴(lài)期)骨髓外成熟(抗原依賴(lài)期)一、骨髓內(nèi)成熟過(guò)程1、骨髓微環(huán)境和B細(xì)胞成熟2、B細(xì)胞成熟的分期3、未成熟自身反應(yīng)性B細(xì)胞的陰性選擇4、Ig基因重排1、骨髓微環(huán)境和B細(xì)胞成熟B細(xì)胞成熟四階段祖B細(xì)胞（proBcells）前B細(xì)胞（preBcells）未成熟B細(xì)胞（immatureBcells）成熟B細(xì)胞（matureBcells）1、骨髓微環(huán)境和B細(xì)胞成熟骨髓基質(zhì)細(xì)胞提供微環(huán)境VCAM-1SCFIL-7基質(zhì)細(xì)胞VLA-4c-KitIL-7R祖B細(xì)胞Earlypro-Bc-KitSCFVLA-4pro-BCytokinesandcell-cellcontactsateac
5、hstageofdifferentiationaredifferentStromalcellCAMVCAM-1Earlypro-BIL-7RStromalcellLatepro-BPre-BIL-7Cytokinesandcell-cellcontactsateachstageofdifferentiationaredifferentBonemarrowstromalcellMaturingBcellsBBStromalcell2、B細(xì)胞成熟的分期分期重鏈輕鏈表面標(biāo)志祖B細(xì)胞(pro-B)（重鏈基因重排）μ胞質(zhì)前B細(xì)胞(pre-B)（輕鏈基因重排）μ替代輕鏈類(lèi)Ig未成熟B細(xì)胞(immature
6、-B)（輕鏈基因重排、陰性選擇）μκ或λｍIgM成熟B細(xì)胞(mature-B)μ+δκ或λｍIgMｍIgD四階段：祖B細(xì)胞前B細(xì)胞未成熟B細(xì)胞成熟B細(xì)胞主要事件：Ig基因重排陰性選擇3、陰性選擇（negativeselection）發(fā)生于未成熟B細(xì)胞若mIgM與基質(zhì)細(xì)胞上的多價(jià)自身抗原結(jié)合，發(fā)生交聯(lián)而致未成熟B細(xì)胞凋亡（apoptosis）若mIgM與單價(jià)可溶性自身抗原結(jié)合，引起自身反應(yīng)性B細(xì)胞無(wú)能(anergy)通過(guò)陰性選擇的未成熟B細(xì)胞繼續(xù)發(fā)育為成熟B細(xì)胞（表達(dá)mIgM和mIgD）Negativeselection-ApoptosisImmatureBcellrecognisesMULTI
7、VALENTselfAgBClonaldeletionbyapoptosisYYBImmatureBYBYYYBAnergicBcellIgDnormalIgMlowImmatureBcellrecognisessolubleselfAgNocross-linkingYYBImmatureBIgMIgDIgDIgDNegativeselection-AnergyYYYYYYMatureBcelle
