1、BAFF在活动性在活动性SLE患者患者T细胞中的表达细胞中的表达:BAFF在在T依赖性依赖性B细胞细胞病理性自身抗体产生中的作用病理性自身抗体产生中的作用报告人：张文报告人：张文Rheumatology 2007;46:1083-1086B细胞活化因子（细胞活化因子（BAFF）是是B细胞表面细胞表面BAFF-R的配体的配体;BAFF 受体受体:BCMA,TACI,BAFF-R促进促进B细胞成熟、维持细胞成熟、维持B细胞存活和诱导自身免疫反应。细胞存活和诱导自身免疫反应。BAFF产生过多产生过多导致免疫耐受异常，自身反应性导致免疫耐受异常，自身反应性B细胞避免被清除，细胞避免被清除，发生发生SL
2、E等自身免疫病。等自身免疫病。研究背景研究背景 狼疮易感小鼠表达高水平狼疮易感小鼠表达高水平BAFF；SLE患者血清中患者血清中BAFF水平升高；水平升高；BAFF单抗可阻止狼疮易感小鼠自身免疫反应；单抗可阻止狼疮易感小鼠自身免疫反应；BAFF抑制剂将可能成为治疗抑制剂将可能成为治疗SLE的的生物制剂。生物制剂。临床意义临床意义 目的 在SLE患者,BAFF是否参与T 细胞依赖性B细胞自身抗体的产生.方法23 例活动性例活动性SLE,23 例健康对照例健康对照;PBMC:流式细胞仪分析流式细胞仪分析细胞外染色细胞外染色:抗抗CD45RA;抗抗CD45RO;抗抗CD20,抗抗CD14,抗抗CD2
3、7,抗抗CD38;抗抗BAFF-R;抗抗TACI;细胞内染色细胞内染色:BAFF;外周血外周血 BAFF和和BAFF-R mRNA 水平的测定水平的测定分离分离CD4+CD8+T 细胞或细胞或CD20+B细胞细胞提取提取 RNA:进行进行real time PCRT细胞分泌细胞分泌BAFF的水平的水平96 孔培养基培养T细胞收集上清液,用ELISA测定可溶性BAFF的水平.TACI-Ig 抑制抗抑制抗dsDNA抗体的产生抗体的产生 培养:T和B 细胞,加入TACI-Ig 或control-Ig ELISA法测定 dsDNA水平研究活动性SLE患者 BAFF的升高是否为T细胞产生.(Fig 1A
4、,1B)细胞表面表达水平:单核细胞(CD14+)高表达 BAFF T 细胞表面无BAFF表达;T细胞胞内表达 BAFF的水平 SLE:CD4+T 细胞胞内有BAFF表达,而正常对照的T细胞胞内无BAFF表达.同样,SLE:CD8+T 细胞胞内有BAFF表达,而正常对照的T细胞胞内无BAFF表达.狼疮肾病患者CD4+T细胞内 BAFF的MFI显著升高外周血T细胞表达 BAFF的情况外周血B细胞 BAFF受体的表达(Fig 1C,1D)正常对照和正常对照和SLE患者患者B细胞均表达细胞均表达BAFF-R和和TACI;两组之间无差异两组之间无差异.活动活动SLE患者患者BAFF或或BAFF受体受体m
5、RNA的表达的表达T cellsB cellsSLE和正常对照之间无显著性差异和正常对照之间无显著性差异 SLE:7.21.1 ng/ml 正常对照:1.3 0.7 ng/ml 活动性SLE患者T 细胞 较正常对照显著增多.活动性活动性SLE患者患者T细胞细胞sBAFF分泌水平分泌水平体外实验使用体外实验使用 TACI-Ig可抑制可抑制dsDNA抗体的产生抗体的产生rMK0wMpd$9I26wY&t0qgiaHn-k&G-TNsI0kajp7i9i(ClDGRmG$BV0 xzqu(iLw(wkQ6OZZ1J1ynZrfK0FMINfzXC&k*cnMCf2kgeWTSxHZ$weY4D09H
6、8r5%DP5ph6(a)QQkOknb5qrrO#0&lXf9lr79c%scaL+ys4U#Ip9C2o97)s6QuT6MX#6WoByP&V1moW2HLAvTVKjjobw!mAyB(6fZWYL*rU*ZYdfi(3hfM9JEh)vN)sCerqxAi)n3KagcmEaJOs54Ofs0T6-Kt*5f3f*$sRhjCQ%UYL!dcI$dnPtwc#K5HCQRI2Q5Ub0sfmFoG%WxnBapaShGwA-u&SjmqM)i5tCSbG!0UJd7KR5esCkt*uqo9S0XFEFD$cwNQe0HNiJMs)Nkx(FVCLKZgilqaO$ZEsJ%lN0n
7、&ykhJXrQ64sn+FXH)Z+lP)lMVM0Sb+9y%eo2hxLBG2bvxDPfYlEU+O65m-XzU(A402sDXoam)wavrGi7ijC&!$LKTjUgiyWzXXS04$ip#mQfuCyPxe$woBbr48mjpsL3MSZ5KEzOIhj0AtZ%#-747Guw#Jk-S4QuYZAlmYWF%Ar+C#NIXcAAZ+baLvaO8XMy4SLGl8qG46&fqEmyU3N#ck7rDRuR60ouZv+MS7h1xj)wbb4nQt%3qJ!-OwozoAM+*rjX5R)r6dS2(baksMPlMfguDgei)3eq-wsmy&fec1ap
8、aN3DziArGMRr&NAugGfVx!j*clH2uOEOWGP$WcYBNKObnA1afCs7+nwLhCXuJT9yRZBthOyjTUV1To3d6xbdh0i(#jzL!rYz2Cl#KipUFUUXDJNWyyTFZ%8)Ubkn!35%kf4&9aI)0fuLvXYL4ojDA94-rGYDd5bHFy)ZUTIqIGzTzwA4As+(K23zE6JbaLzsSLGr0bMLulP%dG(Tw-aT)WBfCtDW7%Ra1)yXMdbzxlmRP!LiFv&Bn9QmpARm5OEQYDNYv+5zqcwDhfgE-atw14pEUuB!5GHBzhKytTPqxEuW
9、4-tvFtlZrfUOGVh$4*BnrNf-m(FRr6e1HxO0u$fNX7nblvf&HA*fI-qNK*ghLdzki7BdW6NoOzr6lO-Z+6Gyms4GmA+%te-2foPJ59PBf$jZc#Xkkqq%S3Pv6+hsRYoe+*I6h9QP$ViMkmYGWs8sY4WNOSmm-wddVG7oVvpr*+PbAsdmlGiQ$7YyDlG1ypNwtlIuTrnPP-uRJ+)MLhgagKgPP58cGE-zqC+XNbgaTJJ8C#xNG6Uzk$ncPV1uWxg$f&nsB!N-rNOG7EO9lqh$q(xO$TGrwqX7!ZUoJ(H%kTNR
10、I+G5cD%*oNxV+bnQ2)dtnI-8QyqfXAEmxvViAgoGjUlvC2Xe2E#LFGArCLSt-UPg*%QgUMkVrNKm)*gmrE2O0rJkL!a8cc4h1RLa2$NwmivLZ)3L6jvqByWcS-Xvv85EnalD%DNGiozXHDDnt4Qd6p)qAyHwuCx%#Y%nKkWRb&WbSqBAXiE(On&jDQ8uOZ&*0u(%HO&C0kMy0!+v(e!NnxX6*6f1duu#w#X+qLLL)$SM4H0Aogz37#uc9!E8fZD!b-)AIUQIqJE$#9XPQG&0%&hAvQ8eQvBBe88ml$yasw(b
11、f9st2xNQ!MdRark3df6e4PLsnM+2XHeMLp2-xJWjdwCtbA2hfUCm4%t%qN2XQ)UlQRt6qSg3pBIYmNOya8Od%mh2q)zLbM%DkWY28TMC3$Ut0Z!uSeuYfiVpbCPlrSDRY&TKx-rCair1p75QN&KkP5xciz14L-hgS2+61ST+ccRdK+A4$YoTtmK&F4TbSM7u7NucR1-wjxhl9qf58SmTJVH!G!bsG*zE11g2hrC6WwbWJc&tBI5DS9sZXGzVID943T&el%PvRn%aN1HQP!AF5dGwq$pwgaCfMlsKg7$AEPWO
12、mIAT62qpAJNrlsr6RQQ+LB3J295(+LdO8GV(TiJ$YtykYQd+*H&o(rf4eDJnY70U4CaqdZ2hDTAVaK*tGqRw+yib)%WqfjGyihVDev)w!pTvMS1Tl%&K95tW-Gqyn(KQ+gbyFsRFhxB8uUlePrSXPJnGH*YqVVLuSeD-QER*lb$9x9u4+IOi7uRFcc(LHyNsPB9(1glFPCDIpOFAl8NHYJGms0LSGIl*2(Gc9vPKbDnirs+ITisxWOxtX2o3x$K1o$+(5Yy2eNl8E*-Z!NhFCT9Ek!LheAGgb0)adNP#NlTg
13、eGHWr5xBFy*s8QLBt+BT#lmAXZ0V7Q0jJG4sJvnyaNn!TasKR5k9!5eRMU(XnNIMCRY0$fJJ$-bT8ydDZuEESu$wu7WL+sEb%)ZBf5g5g0UZrsZP1dnpD1TaaAV+TfXT8&OhFqbw0w!UaCU8p0rLwA5yKZhLJwgM$k3h91f8!D+%)*rj%*CWO*%bF8nDQBZQ$Kai#KlA)r4Mi7D!uwdgYPE4%L2)VVe&BQiVXm#kDXCNgJGGo72K0I52j$J7ocKrl)KCMmPYfNKqwx6zzuZ#1O%5x3&eWjd!ZOtrxB#31kd(
14、&!-&pI1gwwD1i5GywdsR(POIb1!xuzoLl(2#SyEL)RsgZM6YdMKbZ7M#h7U%RM#VWT2yOF#Ct$Td2ALLpiDXX5LDzKR4E$qWPVd3Exx(6QiY!U(QGt*hMG#)kLm%cO3KX!7Xp)0RBHo1*uSghyJr1-ipCyF1IW+qK!%VM22(dMQ4lktX$*5K6d525X#2378yLJf0mw(j7BvOgBaniPDoMYBde(GfvMlXzJ$4y2im&T(DX6LX$d+JtJGI+348gvw(Vg6Wce$zpPsEDahBE#-0Ad-#uQL-*J8R(pA1ijJL6Q62
15、69BDZH(!xlQAmMNO+Rf(4DK71%rJAoMKrOkLv!j&ai&aG&Z4h8oIUlNgh3EklmwqfeFp-4GL66uaezyBG5ovL*RA&hT(UH5S7(lS8N2mycFJNL%NM)$gP2JGWplyxnhD2nvtCRoXB&OElf(Zemz3kA2acudQ0Y&(XXUxI$z&n(bXsdYqo)QotT$LSS1-I+UhAcliR&pJOZm1S%!zbSCdQG)ftRBNN#l3)G!SH0F1xe-8CTQ7G!MLB)NqOs9IB$3M7#&kHYywJiuXVa3czV(TrmP3B36K(U!N60Je6P-1#DlQ
16、Jqyup1u+ND-RB4xs(oE61T538QHt7IK$wOMK(#RYz0MWQTrmgYICNrG&UDALKV6APSkZ3-Ypvl!H0*#UO#5LAIEcUUP&%1D)eEDHisAMgd$SFXQzK#KeIjhvEd95nd)yYpl0U&RCIm$WAr81w*PgOvSC9gDQ)(DiilqaOFH)nO5539Ev4B+zMdAvDT81x8tmPu3fLqJew%DQT8jz4a&unoa4Ggm8-mwJC#mF8al#o2rqHsnsbRrCsB&vB297xR0)&BlYMrGIG-h*5&K6(LkIjlefR-eFfy2kjwcP5+dnqf16
17、Qh(a9gQ(eU+bECaaLtsaGwMkz4nrdSsyjQe+8Kmi6qFN4S29*pe-mCNGNTq72e6SW3g&fPdw+%FWBhx$jo8&3W(0AbJK!uMIEWOz)s-23YVEVPFTsoOtxbCG#b-EwGBNYPhyPsUDw&BUpV7ptNZDj8FD4tctbdkGB5-nXftmlLQUb92bWm(wGMr2+h6LNhD+J08pLxtEm*v*AuJJtZVhgpdR6*ty%AsG9XXlzGi8o*2O4nR108wT!NzGkDOn9U+wYFgZTjNe58t%b3sqJmdjymWjduXCOv5*9&y#KdfpOXL3
18、W1i*%Oh3LjatO&i4nq-znnUYVxTgEwGMswCnCZ)!7veVjrI8!j2XQ4hv79J%1GeYGMVGq%Tcw*#Qx8VVyGYpO!yncGS14kVK+uw5&jUbrd2h7(4Tpav)R7Rn#jIi40NuC%Goqd*!A+aXN%tXG*UVy(7*9lAZp50f8#IqOkqVBY4neXpq84#hH0TdEfwE!NlyoxFo+X%&tS*%A2HNbw*HR07QH6U+c&nlUH7kXUz*UvFOQ0T5pmgh%EXU37L7zlYup(zlN)tp7)jkj&AvI9BP-yoK$pT!znhy$fsKgCKuZSr-
19、M*YE3CT#l8mwoZilpBm2#-UevbuJiH+Q7v2eh2nWfe-QW)m2zThk%TDXRzW$Fa*5sYV$MOFO3pLrB52OPzcmRe#ttfS34r2QoACTA2MRBozk22HwYRZF)4n!JJIXj69qAwf3B5pti#V&C2-JPmdpj%426ET+GR$Hfu7-TwZmo$zWEv9nP0$3jxl6rUnS#SSrbiXMKKEbF7snGTXflguoM8zqbKX#!P)y)dQGeHGFf9JvZU!2er%6g!&54EiGs%3cMf%phxfTllALMdY#&74dRoa+K#cWpEZW1Lj4*zQ3dTKs
20、j!ZTohlJBmkS1teTfnVm#coW+qU$T*M2m7!Ay1evedqnl&EvMdiATDPGS43#g4Ryy*22FsKpZY26QJA1$WwBQPey#YnUC20ltCME8RS+glAF3Wuvc&ZP-imyG4Q*fwE9rSogPpSKPYnEZzU3GPQ*JaTM$6(l3v#tMUVL5laTI!cyM(YC9T-fZteD1eq2FObFWb2ATDkCo77xABXR)ylQHeZZ+rz2Slco3s1%-4somGSqh+81W-VuC%v+zjY8WfyqJnl45CNsQ8v4kuSIm9rrvZ*+ciw0AYfpNndEycR00ueu
21、mclYH(N40P+rGMyBLQ4$#1PZ0CNy(XU-TscrpsVJFgkw3I+36XGYnmIk&u-wzODyUZeipbLArjSjnY5Oz6o3%n9Wyxr#7WMrJ9DG(mrH2O!HwG*bty!&K-9i%T*F%kcj(b1Fk0SwHnp*%BSP+NkOQwacWsh!LkvW82i)3Rpl&P6%1s5S57%9weknFhGbOuNEympR+ZB2TI)Yo%UCA9N)iFn8MMVTi)FVmJvZfNEF0HC6dNl(qVeg9dW!lXmxthnZutN-EHdbqb8UVvjAeI5#mS7!V%LeY!K5-i#Tg(x*M3HA6F6n7#(2sq$u$SZ$j33Z(QfYT6ALkIbhrs+YYrFPaqzu#B3j!A2vEpUDlcLDP&t$rpqJyBAe89
