系统性红斑狼疮患者巨噬细胞表型和功能初步研究

为了比较健康者与SLE患者巨噬细胞表型和吞噬功能的不同,收集性别、年龄匹配的健康对照者及SLE患者外周血,密度梯度离心法分离单个核细胞,磁珠分选CD14+单核细胞,巨噬细胞集落刺激因子诱导7d,分化为成熟巨噬细胞。FACS检测巨噬细胞表面CD163表达。取健康人CD4+T细胞标记CFSE,在抗CD3、CD28抗体刺激下,以5∶1比例分别与SLE和HC巨噬细胞共培养4d,FACS检测CD4+T细胞增殖比例。紫外辐照Jurkat T细胞株诱导人来源凋亡细胞,将pHrodo Green标记的凋亡细胞(5∶1)与SLE和HC巨噬细胞共培养2h,FACS检测pHrodo+CD14+巨噬细胞的百分率。结果显示,与HC相比,SLE巨噬细胞CD163表达量显著下降;SLE巨噬细胞对CD4+T细胞增殖抑制能力显著降低;SLE巨噬细胞对凋亡细胞的吞噬功能显著下降。这些结果提示SLE患者巨噬细胞表型、免疫调节能力和吞噬功能存在异常,可能参与其发病。     

早期细胞凋亡引起活动期狼疮小鼠的B 细胞比例下降

目的:探索活动期MRL/lpr狼疮小鼠中B细胞数量的变化及其调节机制。方法:利用流式细胞仪,首先分析了18周龄活动期MRL/lpr狼疮小鼠与正常C57/B6小鼠脾脏中B细胞的周期和B细胞占脾脏淋巴细胞的百分比;用Annexin V和PI标记方法检测了B细胞及其亚类凋亡情况;进一步磁珠分选纯化小鼠脾脏B细胞,实时定量PCR方法检测相关凋亡基因的表达变化。结果:与C57/B6小鼠相比,活动期MRL/lpr狼疮小鼠的B细胞比例明显减少(P0.01),而凋亡比例显著增加(P0.01),其中B细胞的早期凋亡比例增加(P0.01),而晚期凋亡未改变;凋亡的B细胞包括未成熟和成熟B细胞。进一步发现,活动期狼疮小鼠B细胞中抗凋亡蛋白BIRC3明显降低(P0.01),而促凋亡蛋白BCL2L1和BBC3(PUMA)明显增加(P0.01)。结论:活动期狼疮小鼠B细胞的数目减少及早期凋亡的增加可能归功于抗凋亡与促凋亡蛋白的平衡改变,提示活动期SLE患者B细胞的减少可能与其早期凋亡相关。     

实验性自身免疫性脑脊髓炎小鼠脾脏和肝脏中NKT细胞调变的研究

目的:观察NKT细胞在实验性自身免疫性脑脊髓炎(EAE)小鼠脾脏和肝脏中所占百分比的变化特点,探讨NKT细胞在EAE模型中的免疫调节作用.方法:以MOG35-5521肽诱导C57BL/6小鼠建立EAE模型并进行临床评分.于发病高峰期处死小鼠,分离脾脏和肝脏淋巴细胞,采用免疫荧光染色和流式细胞术(FCM)分析,观察EAE小鼠与正常小鼠脾脏和肝脏中NKT细胞在全部淋巴细胞中所占百分率的变化.结果:在EAE小鼠不同器官中,NKT细胞占淋巴细胞的百分率均较正常小鼠减少.脾脏NKT细胞百分率(%)从正常组2.22±0.14下降到EAE模型组1.94±0.07(P<0.05),肝脏NKT细胞百分率(%)从正常组5.52±2.17下降到2.67±1.41(P<0.05).结论:NKT细胞在EAE模型C57BL/6小鼠脾脏和肝脏中增殖受抑,提示EAE发病可能通过对NKT细胞数量的调节进而影响其对免疫应答的调节.     

SLE的淋巴细胞异常

系统性红斑狼疮(SLE)的淋巴细胞异常,表现为B细胞功能亢进和T细胞缺陷。但引起这些异常的原因以及哪种异常发生在先都尚未明确。本文就SLE动物模型及SLE患者的淋巴细胞异常,怎样参与发病过程加以说明。作为SLE模型动物,有NZB、(NZB×NZW)F_1,MRL/L、BXSB、SWan、M-otheaten等小鼠以及与人类SLE更近似的狗模型,这些都为SLE的研究作出了贡献。各种同系交配小鼠的临床表现和血清学所见,虽然与SLE很相似,但不同系鼠间所表现出     

SAP基因注射干预小鼠SLE样综合征的发生

目的：研究SAP基因注射对SLE发病的干预作用，并进一步探讨SAP发挥作用的可能机制。方法：通过RT-PCR方法克隆SAP基因，构建其真核表达质粒pcDNA3-SAP，观察SAP基因注射对活化淋巴细胞免疫诱导小鼠产生的SLE样综合征的干预作用，以ELISA方法检测抗dsDNA抗体的产生情况，以免疫荧光法检测肾脏免疫复合物沉积；通过巨噬细胞吞噬实验观察SAP与DNA结合后对DNA清除的影响；用增殖实验检测巨噬细胞吞噬SAP结合的DNA后对预致敏淋巴细胞活化的影响。结果：SAP基因注射可有效干预小鼠SLE样综合征的发生，SAP与活化淋巴细胞DNA结合后可明显促进巨噬细胞对DNA的吞噬，并且巨噬细胞吞噬SAP结合的DNA后不引起预致敏淋巴细胞的增殖。结论：提示SAP通过促进DNA等自身抗原的有效清除干预SLE疾病的发生。     

系统性红斑狼疮模型小鼠脾脏细胞凋亡及可能机制

目的:研究系统性红斑狼疮(SLE)模型小鼠的脾脏细胞凋亡及其相关调控机制.方法:采用ConA活化的同系脾脏细胞诱导BALB/c小鼠SLE,通过检测其外周血自身抗体、肾组织病理学改变确定SLE小鼠模型诱导成功.脾脏细胞凋亡的检测采用末端脱氧核苷酸转移酶介导的缺口末端标记法,免疫细胞化学法检测脾脏细胞Bcl-2和NF-кB的表达.结果:ConA活化的同系脾脏细胞成功诱导BALB/c小鼠发生SLE,与盐水对照组和未活化脾脏细胞组比较,SLE模型小鼠脾脏细胞凋亡率明显降低,Bcl-2和NF-кB的表达均增加(P<0.01).结论:SLE模型小鼠脾脏细胞凋亡率降低,可能是通过Bcl-2和NF-кB的表达增加所致.     

Yaa基因与狼疮性BXSB小鼠

:BXSB小鼠是系统性红斑狼疮小鼠 (SLE)模型之一。由于Y染色体上存在Yaa(Ychromosome linkedautoimmuneacceleration ,Yaa)基因能够加速自身免疫反应 ,使得雄性鼠早发病 (earlyonsetofdisease)。但是 ,Yaa基因的作用依赖于狼疮性遗传背景基因的存在 ,并由此导致B细胞和T细胞的表型或功能的变化 ,继而引起致病性自身抗体的产生 ,从而形成BXSB小鼠SLE发病的细胞学基础     

榄香烯复合瘤苗HSP70与HSP70BCG对巨噬细胞功能影响的比较

目的 :比较Hca F榄香烯复合瘤苗HSP70 (HSP70 HTCV)和卡介苗HSP70 (HSP70 BCG)对小鼠腹腔或脾脏巨噬细胞功能的影响 ,分析HSP70 HTCV诱导抗瘤免疫作用的机制。方法 :给正常BALB C小鼠腹腔注射HSP70 HTCV 或HSP70 BCG ,共 3次 ,并用多聚甲醛固定的Hca F细胞体内冲击。收集腹腔和脾脏的巨噬细胞 ,并用HSP70 HTCV或HSP70 BCG 体外再致敏 ,用MTT法测细胞毒活性、细胞的增殖和分泌TNF的能力 ,用中性红吞噬试验测巨噬细胞的吞噬能力。结果 :用HSP70 HTCV 免疫小鼠的腹腔巨噬细胞对Hca F的细胞毒活性强于用HSP70 BCG 免疫小鼠的腹腔巨噬细胞 (4 2 7%VS 31 0 % ,P <0 0 5 ) ;用HPS70 HTCV 免疫小鼠的脾脏巨噬细胞分泌TNF的能力高于用HSP70 BCG免疫小鼠的脾脏巨噬细胞 ,细胞培养上清对L92 9的细胞毒活性分别为 5 7 4 %和 35 9% (P <0 0 5 ) ,脾脏巨噬细胞吞噬中性红的能力的变化两组之间无明显差别 ;免疫巨噬细胞的上述功能均高于未经免疫的对照小鼠的巨噬细胞 (P <0 0 1) ,而三组巨噬细胞的增殖改变无明显差别 (P >0 0 5 )。结论 :HSP70 HTCV 或HSP70 BCG 免疫都能增强巨噬细胞功能 ,但HSP70 HTCV免疫诱导的巨噬细胞对肿瘤细胞有更强的杀伤活性     

间充质干细胞增强巨噬细胞功能治疗SLE实验研究

目的从对巨噬细胞功能调控角度探讨脐带间充质干细胞(umbilical cord mesenchymal stem cells,UCMSC)对狼疮鼠的治疗机制,为临床用于治疗狼疮患者提供理论依据。方法 24周龄B6.MRL-Fas~(lpr)(B6/lpr)狼疮鼠随机分为空白对照组、UCMSC移植治疗组和成纤维样滑膜细胞(fibroblast like synoviocytes,FLS)移植对照组,同周龄雌性C57BL/6鼠作为正常对照。UCMSC和FLS组均给予1×10~6数量尾静脉输注,各组小鼠于28周龄处死。HE检测小鼠肾脏病理,评估疗效。分离纯化小鼠腹腔和肾脏巨噬细胞,无菌条件下取8周龄雌性C57BL/6小鼠脾脏,磁珠分选CD4~+T细胞,在抗CD3/28刺激下,将其以5∶1比例与小鼠巨噬细胞共培养4 d,CFSE法检测CD4~+T细胞增殖。2μm荧光微球与小鼠巨噬细胞共培养2 h,流式细胞术检测巨噬细胞吞噬活性。结果 (1)UCMSC组可显著改善狼疮鼠肾脏病理;(2)UCMSC移植治疗可显著提高狼疮鼠巨噬细胞的免疫调节能力,使其对CD4~+T细胞增殖的抑制能力显著增强;(3)UCMSC组狼疮鼠腹腔巨噬细胞的吞噬功能显著增强。结论 UCMSC移植治疗狼疮鼠可以改善肾脏病理损伤,UCMSC对巨噬细胞免疫调节和吞噬功能的调控是其发挥治疗作用的机制之一。     

具有SLE疾病症状的MRL/lpr小鼠体内自噬水平检测

目的检测16周龄MRL/lpr小鼠发病情况,并研究发病后的MRL/lpr小鼠脾脏自噬水平。方法采用雌性MRL/lpr小鼠和雌性C57BL/6小鼠,分别于16周龄时检测2组小鼠脏器系数,ELISA检测血清抗ds-DNA、ANA的水平,淋巴结、肾脏病理HE染色观察,以检测MRL/lpr小鼠发病情况。取发病小鼠,Western blot检测2组小鼠脾脏自噬相关蛋白Beclin-1、ATG5、P62、LC3Ⅱ/Ⅰ的表达,Real-time PCR检测自噬相关基因Beclin-1、ATG5、Atg12、LC3B mRNA的表达,流式检测2组小鼠脾脏中B细胞和浆细胞的比例。结果 16周龄MRL/lpr小鼠脾脏、淋巴结脏器系数升高,血清中自身抗体水平显著升高,淋巴结和肾脏均出现一定程度的病理性改变。此时脾脏中的自噬相关蛋白Beclin-1、ATG5、LC3Ⅱ/Ⅰ表达均高于C57BL/6小鼠,P62的表达显著低于C57BL/6小鼠,自噬相关基因ATG5 mRNA的表达也显著升高。此外,相较于C57BL/6小鼠,MRL/lpr小鼠脾脏中B细胞数量减少,而抗体分泌型浆细胞数量显著升高。结论 16周龄MRL/lpr小鼠已出现狼疮样症状,出现自噬水平异常升高的现象,并且脾脏中抗体分泌型浆细胞的增多可能与异常升高的自噬水平密切相关。     

中药狼疮方对狼疮样BXSB小鼠脾脏免疫系统和淋巴细胞亚群的影响

目的：研究中药狼疮方对狼疮样BXSB小鼠免疫系统和淋巴细胞亚群的影响，探讨狼疮方治疗SLE的免疫学机制。 方法： 采用BXSB小鼠模型，随机分为3组：狼疮方治疗组（每天0.5 mL狼疮方药液灌胃）、强的松治疗组（每天prednisone 0.173 mg/20 g BW溶于0.5 mL生理盐水灌胃），未治疗组（每天0.5 mL生理盐水灌胃），每组6只，疗程10周。另设与BXSB小鼠同基因的正常C57BL/6小鼠6只为正常对照组。分别采集上述各组小鼠外周血和脾组织进行检测。 结果： （1）未治疗组BXSB小鼠血清IgG和抗ds-DNA抗体水平及脾组织CD3、CD4、CD8、CD19、CD23阳性细胞百分比都显著高于正常对照组、狼疮方治疗组、强的松治疗组（P＜0.05或P＜0.01）。（2）经狼疮方或强的松治疗后，BXSB小鼠血清IgG、抗ds-DNA抗体水平及脾组织CD4、CD8、CD19、CD23阳性细胞百分比显著低于未治疗组（与未治疗组相比，P＜0.05或P＜0.01），且接近正常水平（与正常对照组比较，P＞0.05）。 结论： 狼疮样BXSB小鼠T、B细胞免疫功能上调。中药狼疮方可抑制狼疮样小鼠T、B淋巴细胞活化，减轻其高丙种球蛋白血症，减少体内自身抗体产生。     

Antigen-induced B cell apoptosis is independent of complement C4

Deficiencies in early complement components are associated with the development of systemic lupus erythematosus (SLE) and therefore early complement components have been proposed to influence B lymphocyte activation and tolerance induction. A defect in apoptosis is a potential mechanism for breaking of peripheral B cell tolerance, and we hypothesized that the lack of the early complement component C4 could initiate autoimmunity through a defect in peripheral B lymphocyte apoptosis. Previous studies have shown that injection of a high dose of soluble antigen, during an established primary immune response, induces massive apoptotic death in germinal centre B cells. Here, we tested if the antigen-induced apoptosis within germinal centres is influenced by early complement components by comparing complement C4-deficient mice with C57BL/6 wild-type mice. We demonstrate that after the application of a high dose of soluble antigen in wild-type mice, antibody levels declined temporarily but were restored almost completely after a week. However, after antigen-induced apoptosis, B cell memory was severely limited. Interestingly, no difference was observed between wild-type and complement C4-deficient animals in the number of apoptotic cells, restoration of antibody levels and memory response.     

Isolation and functional analysis of autoreactive T cells from BXSB mice with murine lupus

CD4(+) T helper cells play a pivotal role in the pathogenesis of SLE, although the mechanism is still unclear. The present study was designed to isolate and characterize autoreactive T lymphocytes from BXSB mice, a mouse model for human SLE. Splenocytes from 6-month-old male BXSB mice with murine lupus were repeatedly stimulated in vitro with irradiated syngeneic B cells in the presence of recombinant IL-2, resulting in six autoreactive T-cell lines and two T-cell clones. TCR analysis showed that, one of the T-cell lines, ATL1, was almost clonal, as a Vbeta2.1-Jbeta2, a Valpha5.1-Jalpha15 and a Valpha10.1-Jalpha15 chains were predominantly expressed in this line. The two clones derived from ATL1 turned out to be sister clones, using the TCR Vbeta2.1-Jbeta2 and Valpha10.1-Jalpha15 chains. ATL1 cells proliferated in response to stimulation of syngeneic and H-2-matched allogeneic B cells and secreted IFN-gamma. Monoclonal Ab against CD4 and CD28 inhibited the proliferative response of ATL1 for syngeneic B cells. Interestingly, ATL1 did not respond to BXSB spleen or peritoneal macrophages, suggesting that B cells were able to either express accessory molecules necessary for T-cell triggering or present cryptic epitopes recognized by the autoreactive T cells. Moreover, ATL1 was able to help BXSB, but not C57BL/6, B cells producing IgG and IgM Abs against dsDNA and histone in vitro. Passive transfer of viable ATL1 cells into young female BXSB mice significantly accelerated the production of autoantibodies. Possible mechanisms of interaction between ATL1 and lupus B cells are further discussed.     

Expanded macrophage precursor populations in BXSB mice: possible reason for the increasing monocytosis in male mice.

The BXSB mouse spontaneously develops an autoimmune disease that resembles human systemic lupus erythematosus (SLE). During their lifetime, male BXSB mice show an increasing monocytosis in the peripheral blood as opposed to their female littermates. This monocytosis is unique among autoimmune-prone mice. To test the hypothesis that alterations at the stem cell level may be responsible for this monocytosis, myeloid bone marrow precursor cells were examined in both male and female BXSB mice from 4 to 40 weeks of age. The number of M-CSF responding stem cells (CFU-M) and the number of GM-CSF responding stem cells (CFU-GM) were higher than in all other inbred mouse strains tested. In addition, male BXSB mice developed a progressive increase of CFU-M and CFU-GM in the bone marrow during their lifetime, which paralleled the peripheral blood monocytosis. The monocytosis in male BXSB mice is the result of a further expansion of the strain-specific high number of macrophage precursors by intrinsic factors, which may be attributed to the influence of the Yaa factor. The sex-specific expanded mononuclear phagocyte system may promote the autoimmune process and may be one reason for the dramatic course of murine SLE in male BXSB mice.     

Apoptosis and the thymic microenvironment in murine lupus.

The thymus of New Zealand black (NZB) mice undergoes premature involution. In addition, cultured thymic epithelial cells from NZB mice undergo accelerated preprogrammed degeneration. NZB mice also have distinctive and well-defined abnormalities of thymic architecture involving stromal cells, defined by staining with monoclonal antibodies specific for the thymic microenvironment. We took advantage of these findings, as well as our large panel of monoclonal antibodies which recognize thymic stroma, to study the induction of apoptosis in the thymus of murine lupus and including changes of epithelial architecture. We studied NZB, MRL/lpr, BXSB/Yaa, C3H/gld mice and BALB/c and C57BL/6 as control mice. Apoptosis was studied both at basal levels and following induction with either dexamethasone or lipopolysaccharide (LPS). The apoptotic cells were primarily found in the thymic cortex, and the frequency of apoptosis in murine lupus was less than 20% of controls. Moreover, all strains of murine lupus had severe abnormalities of the cortical network. These changes were not accentuated by dexamethasone treatment in cultured thymocytes. However, the thymus in murine lupus was less susceptible to LPS-induced apoptosis than control mice. Finally we note that the number of thymic nurse cells (TNC) was lowest in NZB mice. Our findings demonstrate significant abnormalities in the induction of apoptosis and the formation of TNC-like epithelial cells in SLE mice, and suggest that the abnormalities of the thymic microenvironment have an important role in the pathogenesis of murine lupus.     

BXSB小鼠外周B淋巴细胞凋亡的初步研究

外周Ｂ细胞异常增生是系统性红斑狼疮（ＳＬＥ）突出的免疫学异常表现之一。近年来愈来愈多的研究表明淋巴细胞凋亡异常与包括ＳＬＥ在内的多种自身免疫病的发生有关。本文采用ＴＵＮＥＬ法结合流式细胞分析技术，对ＳＬＥ模型－ＢＸＳＢ小鼠脾脏中Ｂ细胞凋亡的情况进行了检测，发现该小鼠脾脏Ｂ细胞凋亡发生率明显高于正常对照小鼠。提示Ｂ细胞凋亡异常可能与ＳＬＥ小鼠Ｂ细胞的异常增生有关。     

脱氢表雄酮对狼疮性BXSB小鼠脾脏淋巴细胞凋亡的影响

目的 研究脱氢表雄酮(DHEA)对BXSB狼疮性小鼠脾脏淋巴细胞凋亡的影响,并探讨其作用机理.方法 运用流式细胞术、免疫双荧光染色法检测脾脏淋巴细胞凋亡.结果 当DHEA的浓度为10-8mol/L时,淋巴细胞凋亡率降低,与对照组比较有差异有统计学意义(P＜0.05),细胞坏死率差异无统计学意义(P＞0.05);DHEA与西药组或中药组联合应用对淋巴细胞凋亡抑制作用更加显著,差异有统计学意义(P＜0.01).结论 脱氢表雄酮可明显抑制BXSB小鼠脾脏淋巴细胞凋亡率.     

Inhibitory IgG Fc receptor promoter region polymorphism is a key genetic element for murine systemic lupus erythematosus

The autoimmune-type Fcgr2b with deletion polymorphism in AP-4-binding site in the promoter region is suggested to be one most plausible susceptibility gene for systemic lupus erythematosus (SLE). We previously found that there is a strong epistatic interaction between the autoimmune-type Fcgr2b polymorphism and Y chromosome-linked autoimmune acceleration (Yaa) mutation, thus severe SLE observed in BXSB males neither develops in BXSB females nor in the congenic BXSB.IIB^B6 males carrying wild C57BL/6-type Fcgr2b. Present studies examined whether the wild-type Fcgr2b could suppress SLE in mice carrying Yaa-unrelated SLE susceptibility genes. Comparison of disease features between SLE-prone (NZW × BXSB) F1 females and the congenic (NZW × BXSB.IIB^B6) F1 females carrying wild-type Fcgr2b showed that, as compared with findings in the former, SLE features including activation/proliferation of not only B cells but also T cells and monocytes/macrophages were all inhibited in the latter. It was concluded that the autoimmune-type Fcgr2b promotes and the wild-type inhibits SLE through mechanisms that promote and suppress activation/proliferation of a wide variety of immune cells, respectively. Thus, the Fcgr2b polymorphism is a key genetic element for not only Yaa-related but also Yaa-unrelated lupus.     

NF-κB信号途径在小鼠狼疮性肾炎发病中的可能作用

目的:探讨NF-κB信号途径在小鼠狼疮性肾炎发病中的可能作用。方法:选取16周龄的雄性BXSB小鼠(狼疮性肾炎模型组)和同周龄C57BL/6小鼠(正常对照组)作为研究对象,透射电镜和PAS染色观察肾组织的超微结构形态改变;RT-PCR技术检测小鼠全血中HMGB1mRNA的表达变化。采用ELISA方法检测血清中HMGB1蛋白浓度;免疫组织化学检测肾组织中HMGB1和PCNA蛋白的表达变化;Western blot和流式细胞术检测肾组织中RAGE、p-NF-κB和IκB蛋白的表达。结果:16周时,与正常的C57BL/6小鼠相比,BXSB小鼠血清中BUN水平及尿中微球白蛋白水平明显升高;与正常的C57BL/6小鼠相比,BXSB小鼠全血中HMGB1mRNA水平和血清中HMGB1蛋白浓度明显升高;16周时,与正常的C57BL/6小鼠相比,BXSB基底膜明显增厚,部分足突融合,内皮细胞下可见团块状电子致密物沉积;与正常的C57BL/6小鼠相比,BXSB小鼠肾组织的肾小球中可见较多的PCNA阳性表达,肾小管上皮细胞核内也可见少量的表达;BXSB小鼠肾组织中HMGB1蛋白表达升高,HMGB1蛋白尤其在细胞增生明显而肥大的肾小球呈高表达,主要位于细胞浆和细胞外;而在C57BL/6小鼠肾脏组织中以小管细胞核表达为主;与对照组相比,BXSB小鼠肾组织p-NF-κB和RAGE蛋白表达明显升高;而IκB蛋白表达明显降低;HMGB1蛋白与p-NF-κB蛋白表达呈显著正相关(r=0.833,P=0.000);p-NF-κB蛋白与RAGE蛋白表达呈显著正相关(r=0.621,P=0.018);HMGB1蛋白与RAGE蛋白表达呈显著正相关(r=0.848,P=0.000);p-NF-κB蛋白与IκB蛋白表达呈显著负相关(r=-0.759,P=0.002)。结论:HMGB1在小鼠狼疮性肾炎中的致炎作用可能部分通过结合其受体RAGE,激活NF-κB信号途径,促进肾小球固有细胞的增生,从而导致增生性肾小球肾炎形成而实现的。     

BXSB小鼠血清抗DNA抗体水平及其对淋巴细胞转化的影响

用酶联免疫吸附剂测定法（ＥＬＩＳＡ）和３Ｈ－胸腺嘧啶核苷掺入法，观察一种自发性系统性红斑狼疮（ＳＬＥ）好发小鼠（ＢＸＳＢ小鼠）在不同月龄时，血中抗ＤＮＡ抗体水平的变化，并观察该血清对正常ＬＡＣＡ小鼠淋巴细胞转化的影响。结果显示，自３月龄起，ＢＸＳＢ雄性鼠血中的抗ＤＮＡ抗体水平开始升高，４月龄上升至高峰，５月龄仍保持较高水平，各月龄ＢＸＳＢ血清与对照血清相比，Ｐ＜０．０５（ＡＮＯＶＡ）。同时，该血清对正常ＬＡＣＡ小鼠淋巴细胞转化也有抑制作用，以４月龄血清的抑制作用最大。如果将同一只小鼠血清抗ＤＮＡ抗体水平的变化与该血清对淋巴细胞转化的影响做回归和相关分析，发现两者有明显的正相关关系（，０．２３２，＜一５３，尸＜Ｏ．０５）。提示雄性＊ｘ８Ｂ小鼠可能从３月龄开始表现ＳＬＥ。发病后，血清中产生某种能够抑制淋巴细胞转化的物质，它的产生与抗ＤＮＡ抗体有平行关系。