hCGβ-C3d3基因免疫BALB/c小鼠选择性促进B细胞克隆扩增

评价分子佐剂C3d在基因免疫中选择性促进抗原特异性B细胞增殖作用。分别用质粒pCMV4-hCG-βC3d3和pCMV4-hCGβ免疫BALB/c小鼠,免疫剂量为50 pmol。间隔3周相同剂量加强免疫1次。加强免疫后第1周及第2周,MTT法分析各组小鼠脾脏B细胞和T细胞增殖;ELISPOT法分析两免疫组小鼠脾脏hCGβ抗原特异性IgG分泌细胞。结果显示在加强免疫后第1周及第2周,hCG-βC3d3免疫组B细胞增殖能力显著高于hCGβ免疫组及正常对照组;而各组间T细胞增殖状况未见明显差异。hCG-βC3d3免疫组较hCGβ免疫组小鼠脾细胞分泌IgG的量和分泌hCGβ抗体的细胞数量均明显增加。结果表明分子佐剂C3d对于B细胞具有选择性克隆扩增作用。     

华蟾素对Hela细胞生长和小鼠脾淋巴细胞分泌IL-2的影响

目的研究华蟾素对体外培养Hela细胞生长抑制作用及其对小鼠脾淋巴细胞分泌IL-2水平的影响,探讨其抑癌作用机理.方法采用MTT法检测华蟾素对体外培养的Hela细胞生长抑制作用,体外分离纯化小鼠脾淋巴细胞,PHA-P刺激其增殖分化,并和不同浓度的华蟾素共培养,双抗体夹心ABC-ELISA法检测分泌IL-2的水平.结果华蟾素在0.062 5～0.5 μg/mL组间、24～96h时间组间对Hela生长抑制作用均有显著性意义(P＜0.05),0.5 μg/mL华蟾素与对照组间差异有显著性意义.比较0.062 5～0.5 μg/mL的华蟾素对小鼠脾淋巴细胞分泌IL-2水平的影响,各质量浓度组间差异均有显著性意义(P＜0.05),0.25、0.5 μg/mL的华蟾素与对照组间差异有显著性意义,0.062 5、0.125 μ~mL的华蟾素与对照组间差异无显著性意义.结论华蟾素能够抑制Hela细胞的体外生长,且能促进脾淋巴细胞分泌IL-2,从而增强T细胞免疫功能,诱导肿瘤免疫可能是华蟾素抗肿瘤的重要机制之一.     

hCGβ-03d3基因免疫BALB／c小鼠选择性促进B细胞克隆扩增

评价分子佐剂C3d在基因免疫中选择性促进抗原特异性B细胞增殖作用。分别用质粒pCMV4-hcGβ-C3d3和pCMV4-hOGβ免疫BALB／c小鼠，免疫剂量为50pmol。间隔3周相同剂量加强免疫1次。加强免疫后第1周及第2周，MTT法分析各组小鼠脾脏B细胞和T细胞增殖；ELISPOT法分析两免疫组小鼠脾脏hcGβ抗原特异性IgG分泌细胞。结果显示在加强免疫后第1周及第2周，hCGβ-C3d3免疫组B细胞增殖能力显著高于hCGβ免疫组及正常对照组；而各组间T细胞增殖状况未见明显差异。hcGβ-C3d3免疫组较hCGβ免疫组小鼠脾细胞分泌IgG的量和分泌hCGβ抗体的细胞数量均明显增加。结果表明分子佐剂C3d对于B细胞具有选择性克隆扩增作用。     

重组Bla g2变应原诱导小鼠变态反应气道炎症动物模型的建立

目的建立重组德国小蠊变应原Bla g2（rBla g2）诱导的小鼠变态反应气道炎症动物模型.方法在大肠杆菌中诱导表达Bla g2重组蛋白,用镍亲和柱层析法提纯重组蛋白;24只BALB/c小鼠随机分为德国小蠊粗浸液组（A组）、德国小蠊粗浸液＋重组Bla g2组（B组）、重组Bla g2（C组）、阴性对照组（D组）.分别通过HE染色和PAS染色（periodic acid-Schiff）观察小鼠肺部炎症和黏液分泌;观察支气管肺泡灌洗液（BALF）中细胞总数和细胞分类;用酶联免疫吸附试验（ELISA）检测BALF、脾细胞培养上清的细胞因子和血清rBla g2特异的IgE、IgG1、IgG2a抗体.结果成功表达、纯化Bla g2重组蛋白;A、B与C组肺部病理改变呈现明显的变态反应性炎症;BALF中的细胞总数、中性粒细胞数、EOS计数、IL-4、血清抗原特异性IgE抗体、IgG1抗体和脾细胞分泌IL-4均显著高于阴性对照组（P＜0.01）.结论用rBla g2能成功建立小鼠变态反应气道炎症动物模型.     

抗CRP杂交瘤单克隆抗体的制备及研究

应用杂交瘤技术融合Sp2/0瘤细胞与CRP免疫的BALB/c小鼠脾细胞,经选择培养和细胞克隆,建立了4株抗CRP特异性单克隆抗体分泌细胞株242B3、242C4、263A5与263B5,其染色体均在Zn=62～67间,抗体Ig鉴定分别为IgG2a、IgG2a、IgG2b和IgG2b腹水抗体效价为1～3×10~(-5)。     

热致死发酵乳杆菌对牛乳β-乳球蛋白过敏小鼠的免疫调节作用

目的:观察热致死的发酵乳杆菌对牛乳β-乳球蛋白(BLG)致敏小鼠Th1/Th2细胞平衡、血清抗体水平及T细胞亚群数量的影响,探讨其缓解过敏反应的作用。方法:用牛乳BLG和弗氏佐剂的混合液腹腔注射诱发BALB/c小鼠致敏,建立动物过敏模型。将实验动物随机分为空白组、致敏组和不同剂量的热致死发酵乳杆菌组。采用ELISA法测定各组小鼠血清总IgE、BLG特异性IgE和总IgG含量。体外分离培养各组小鼠脾细胞,采用ELISA法检测细胞上清液中Th1型细胞因子(IL-12、IFN-γ)和Th2型细胞因子(IL-4)水平,采用流式细胞术检测脾淋巴细胞中CD3+、CD4+和CD8+T百分含量。结果:发酵乳杆菌组小鼠脾细胞培养上清液中IFN-γ/IL-4比值为13.53,显著高于致敏组的3.34(P<0.05);血清总IgE、BLG特异性IgE和总IgG水平显著降低(P<0.05);脾细胞中CD3+和CD4+T细胞比例升高,CD4+/CD8+比值趋近正常组。特别是高剂量的热致死发酵乳杆菌组小鼠脾细胞培养上清液中抑制IL-4分泌的效果显著优于致敏组(P>0.05),且该组小鼠血清的抗体水平和CD4+/CD8+比值与空白组相比无差异(P>0.05)。结论:热致死的发酵乳杆菌干预可改善小鼠的BLG过敏症状,其作用可能与促进Th1占优势的Th1/Th2细胞平衡,阻断IgE、IgG分泌及平衡T细胞亚群数量相关。     

地龙提取物对小鼠腹腔MФ和脾细胞NO及TNF-α产生的影响

目的 :探讨地龙提取物 (AL)对小鼠腹腔MΦ 和脾细胞分泌NO和TNF α的影响。方法 :将不同剂量的AL与小鼠腹腔MΦ 或脾细胞孵育 2 4h ,收集上清液分别采用重氮化反应和MTT比色法 ,检测NO和TNF α的水平。结果 :0 .1g/L的AL组与正常对照相比较 ,可明显提高MΦ 和脾细胞分泌NO的水平 ,并可以拮抗地塞米松 (Dex)对MΦ 和脾细胞分泌NO的抑制作用。 1× 10 -4,1× 10 -3 g /L的AL组可促进MΦ 和脾细胞分泌TNF α ,并可拮抗Dex的抑制作用。结论 :AL可以激活ΜΦ 和脾细胞 ,使其分泌NO和TNF α的水平增加 ,并可拮抗Dex对ΜΦ 和脾细胞的抑制作用。     

抗人BPI23单克隆抗体的制备和鉴定

目的 采用杂交瘤技术制备抗人BPI23单克隆抗体,并对其应用进行初步分析。方法 免疫小鼠脾细胞与小鼠骨髓瘤细胞按常规方法融合;用间接ELISA法和Western - blot筛选分泌抗体的杂交瘤细胞株;阳性克隆用有限稀释法亚克隆3次获得稳定分泌抗人BPI23单克隆抗体的杂交瘤细胞株;扩增杂交瘤细胞注入小鼠腹腔后制备腹水;纯化腹水中的单抗并对抗体类型进行鉴定;用Western-blot分析抗体的特异性;用间接ELISA法测抗体效价;将分离纯化的正常人外周血中性粒细胞和单个核细胞制成涂片,用抗人BPI23单克隆抗体进行免疫染色。结果 获得3个（1B4、9C12和2H11）稳定分泌抗人BPI23单克隆抗体的杂交瘤细胞株,所分泌的单抗类型分别为κ型IgM、κ型IgG1和κ型IgG1;抗体效价分别为1.28×105、1.28×105和4.1×106,纯化后抗体含量分别为0.208g/L、2.03g/L和3.88g/L;3种纯化抗体均能与本实验制备的人BPI23和市售人BPI55标准品特异性结合,而不能与小鼠BPI25和人LBP结合;在免疫组化实验中,1B4、9C12和2H11单抗均能与人中性粒细胞中的BPI特异性结合。结论 成功制备了人BPI23特异性单克隆抗体,为BPI检测试剂盒的研制奠定了基础。     

超抗原SEA活化淋巴细胞抗肿瘤活性的实验研究

纯化SEA在 10 -12 ～ 10 -5g/ml浓度范围对体外培养的BALB/c鼠脾细胞表现了细胞增殖诱导能力 ,并呈剂量依赖关系 ,其中 10 -7～ 10 -5g/mlSEA的作用强于最适量 ( 2 5 μg/ml)PHA。在E/T为 5∶1～ 2 0∶1条件下 ,10 -5g/mlSEA活化 48h的BALB/c鼠脾细胞对YAC 1细胞的杀伤活性高于NK细胞 ,但SEA未能增强BALB/c鼠脾细胞对B16细胞的杀伤活性。 5 μg和5 0 μgSEA体内用药对L615白血病无治疗作用 ,但转输经SEA活化的同系小鼠脾细胞对L615白血病有一定疗效。实验结果提示 ,SEA活化淋巴细胞对NK敏感的淋巴瘤、白血病有杀伤及治疗作用 ,这种作用依赖于较大数量级SEA活化淋巴细胞的存在 ,并且与SEA活化T细胞分泌的细胞因子有关     

丙型肝炎病毒重组蛋白抗原联合免疫的免疫原性和保护性研究

目的 研究两个丙型肝炎病毒(HCV)多表位重组抗原联合免疫后诱导的细胞免疫和体液免疫应答,以及对小鼠的保护作用.方法 用两个多表位抗原HCV-T和HCV-E1联合免疫BALB/c小鼠3次,ELISA检测血清中抗体IgG、IgG1和IgG2a滴度;最后一次免疫后10 d杀死一半小鼠,取脾细胞,用乳酸脱氢酶(LDH)释放法检测细胞毒性T淋巴细胞(CTL)活性;ELISPOT法检测分泌IFN-γ和IL4的细胞;最后一次免疫后2周,在免疫小鼠的背部皮下注射106个SP2/0-NS3细胞,考察联合免疫对小鼠的保护作用;另取BALB/c小鼠,先在背部皮下注射106个SP2/0-NS3细胞,7 d后开始联合免疫,免疫3次,考察免疫治疗作用.结果 用HCV-T+HCV-E1联合免疫诱导了高滴度的HCV-E1特异性的IgG、IgG1和IgG2a抗体以及高水平的CTL活性;与单独免疫相比,联合免疫产生的分泌IFN-γ和IL-4的细胞数量有协同作用;而且联合免疫能有效预防和治疗SP2/0-NS3对小鼠的攻击.结论 HCV-T+HCV-E1联合免疫诱导了保护性的体液免疫和细胞免疫应答,有望进一步开发为一种有效的重组HCV疫苗.     

LPS刺激诱导人卵巢癌细胞株Toll样受体4表达及细胞免疫调节

目的 探讨脂多糖(LPS)刺激对体外培养的人卵巢癌细胞株SKOV3的生长、Toll样受体4(TLR4)的表达、细胞活性氧(ROS)表达及6种炎性细胞因子分泌水平变化的影响.方法 用流式细胞仪测定不同浓度LPS刺激SKOV3 4 h后TLR4的表达水平;用LPS分别刺激SKOV3细胞不同时间后,MTT法检测细胞增殖情况,流式细胞仪分析TLR4表达、细胞周期分布、ROS表达水平以及细胞因子分泌水平.结果 TLR4表达与LPS作用浓度之间存在浓度依赖性和最大量效曲线关系;LPS刺激组与正常组的细胞增殖、细胞周期PrI值(细胞增殖指数,S+G_2/M)、ROS表达水平、细胞因子分泌水平均有显著性差异.结论 LPS具有诱导卵巢癌细胞TLR4表达、活性氧表达、炎症因子分泌以及细胞增殖和抑制的作用.     

Effect of Anticancer Drugs on the Release of Tgf-β In Vitro

Some conventional and experimental anticancer drugs were tested for their effect on Concanavalin A (Con A) -induced Transforming Growth Factor-β (TGF-β) release from BALB/c splenocytes, lipopolysaccharide (LPS)-induced TGF-β release from Nude mouse splenocytes and BALB/c peritoneal exudate cells stimulated by LPS in vitro.

When 5×10⁶ BALB/c and Nude mouse splenocytes/ml stimulated with 1μg/ml Con A, 50ng/ml LPS respectively, and 5×10⁶/ml peritoneal exudate cells stimulated with 50ng/ml LPS were incubated with various non-cytotoxic concentrations of the vinca alkaloid Vincristine, there was an inhibition of the release of TGF-β in culture supernatants of both BALB/c splenocytes and peritoneal exudate cells. But, in Nude mouse Vincristine did not alter the release of TGF-β.

The antitumour antibiotic Bleomycin, the immunoactive peptide FK565 and the immunosuppressive agent Cyclosporin A (CsA) were found to have no effect on the release of TGF-β from all culture supernatants.     

脂多糖通过NF-κB途径上调大鼠腹膜间皮细胞表达CD40和ICAM-1

目的 观察脂多糖(LPS)作用下大鼠腹膜间皮细胞NF-κB活性及其对CD40和细胞间黏附分子1(ICAM-1)表达的影响.方法 分离及培养大鼠腹膜间皮细胞.LPS不同浓度作用12 h 及LPS (5 μg/ml)作用不同时间点收集细胞;LPS(5 μg/ml)或BAY11-7085(一种IκBα的磷酸化抑制剂)不同浓度(1 μmol/L和5 μmol/L)预处理3 h加LPS,作用3 h后收集细胞;采用RT-PCR方法检测CD40和ICAM-1 mRNA表达.采用蛋白印迹检测NF-κB和磷酸化NF-κB(p-NF-κB)蛋白表达.结果 与常规培养基对照组相比,5 μg/ml LPS组CD40和ICAM-1 mRNA表达显著升高(P<0.05),10 μg/ml LPS组显著高于5 μg/ml LPS作用组(P<0.05).5 μg/ml LPS 作用下,ICAM-1 mRNA表达从1 h开始升高,3 h达到高峰,之后逐渐降低.CD40 mRNA表达在1 h无显著变化,3 h时迅速达到高峰,之后逐渐降低.常规培养的大鼠腹膜间皮细胞结构性表达p-NF-κB蛋白;加入LPS后,p-NF-κB蛋白表达显著增加,其中30 min～1 h表达最强,之后逐渐降低,至2 h仍显著高于常规培养组(P<0.05).加入5 μmol/L BAY11-7085后,LPS诱导的CD40和ICAM-1 mRNA表达显著降低(P<0.05),与正常对照组相比差异无统计学意义. 结论 LPS以时间依赖和浓度依赖模式上调CD40和ICAM-1的表达.NF-κB信号途径参与调节LPS诱导的大鼠腹膜间皮细胞CD40和ICAM-1的表达.     

Effect of Anticancer Drugs on the Release of Tgf-β In Vitro

Abstract

Some conventional and experimental anticancer drugs were tested for their effect on Concanavalin A (Con A) -induced Transforming Growth Factor-β (TGF-β) release from BALB/c splenocytes, lipopolysaccharide (LPS)-induced TGF-β release from Nude mouse splenocytes and BALB/c peritoneal exudate cells stimulated by LPS in vitro.

When 5×10⁶ BALB/c and Nude mouse splenocytes/ml stimulated with 1μg/ml Con A, 50ng/ml LPS respectively, and 5×10⁶/ml peritoneal exudate cells stimulated with 50ng/ml LPS were incubated with various non-cytotoxic concentrations of the vinca alkaloid Vincristine, there was an inhibition of the release of TGF-β in culture supernatants of both BALB/c splenocytes and peritoneal exudate cells. But, in Nude mouse Vincristine did not alter the release of TGF-β.

The antitumour antibiotic Bleomycin, the immunoactive peptide FK565 and the immunosuppressive agent Cyclosporin A (CsA) were found to have no effect on the release of TGF-β from all culture supernatants.     

小鼠脾淋巴细胞可能存在5HT_3受体

本文用3H TdR掺入法和MTT法观察 5HT3受体激动剂 1 phenylbiguanide(PBG )、 5HT3受体拮抗剂格拉司琼 (granisetron )和托烷司琼 (tropisetron )对体外培养ICR小鼠脾淋巴细胞ConA ,LPS刺激的增殖和NK细胞活性的影响。结果表明PBG ( 10 6～ 10 4mol/L )抑制ConA刺激的脾细胞增殖反应和脾细胞IL 2的生成 (P <0 0 5 ) ;增强LPS剌激的脾细胞增殖反应 (P <0 0 5 ) ;格拉司琼和托烷司琼双相影响 ,即在低浓度 ( 10 7～ 10 6 mol/L )促进、在较高浓度 ( 10 5～ 10 4mol/L )抑制ConA刺激的增殖反应 (P <0 0 5 ) ;二药均浓度依赖抑制LPS刺激的脾细胞增殖效应。PBG对脾淋巴细胞增殖的影响被同时加入格拉司琼或托烷司琼拮抗 ,格拉司琼和托烷司琼减弱PBG 10 5mol/L对脾细胞增殖反应的影响。本实验 5HT3受体激动剂或拮抗剂浓度不明显影响脾NK细胞活性和无丝裂原刺激的增殖反应。结果提示小鼠脾T细胞和B细胞表面可能存在对淋巴细胞增殖有不同影响的 5HT3受体     

In vitro and in Vivo inhibition of immunoglobulin secretion by the immunosuppressive compound HR325 is reversed by exogenous uridine

The objective was to demonstrate that the immunosuppressive agent HR325 (an inhibitor of dihydroorotate dehydrogenase, DHODH) inhibits immunoglobulin (Ig) secretion both in vitro and in vivo and that this effect can be reversed with exogenous uridine. In vitro, Ig secretion from mouse splenocytes was induced by lipopolysaccharide (LPS) for 5 days. HR325 inhibited the secretion of IgM and IgG with IC50 values of 2.5 and 2 microm, respectively. Adding uridine (50 microm) increased these values to 70 and 60 microm, respectively. Similarly, the IC50 values of another DHODH inhibitor, brequinar sodium, were also attenuated by uridine from 0.04 to 1 microm for IgM, and 0.012 to 10 microm for IgG. HR325 (and a structural analogue A771726) inhibited LPS-induced kappa light-chain cell surface expression on 70Z/3 cells, a property also reversed by uridine. In vivo, the secondary anti-sheep red blood cell (SRBC) antibody response (unaffected by uridine alone) was inhibited by HR325 and brequinar with respective ID50 values of 38 and 0.6 mg/kg per oral (p.o.). Immunosuppression with HR325 (50 mg/kg) and brequinar (1 mg/kg) was abrogated by uridine. Uridine had no effect on cyclophosphamide-induced (10 mg/kg p.o.) immunosuppression. These data are consistent with the immunosuppressive mechanism of HR325 being the result of pyrimidine depletion in vitro and in vivo.     

狼疮鼠骨髓树突状细胞的分离培养和免疫学特性

目的对狼疮鼠骨髓树突状细胞进行分离、培养并分析其免疫学特性,为进一步研究和应用狼疮鼠骨髓来源树突状细胞（DC）奠定基础。方法分离、纯化6周龄雄性BXSB狼疮鼠骨髓单核细胞,以含10%胎牛血清、2ng/ml重组小鼠粒细胞-巨噬细胞集落刺激因子（GM-CSF）和20ng/ml重组小鼠白细胞介素-4的RPMI-1640培养基培养,以脂多糖（LPS,1μg/ml）刺激24h体外诱导BXSB狼疮鼠骨髓细胞分化为DC,倒置显微镜动态观察细胞形态学变化,流式细胞仪分析细胞表面分子,混合淋巴细胞反应检测其刺激T细胞增殖能力。结果经体外诱导培养第2～8天可见大量细胞集落形成,培养的DC具有典型树突状形态,同时DC可显著刺激同种异体混合淋巴细胞增殖。结论体外诱导培养可稳定获得BXSB狼疮鼠骨髓来源DC。     

Purified lipopolysaccharide from Francisella tularensis live vaccine strain (LVS) induces protective immunity against LVS infection that requires B cells and gamma interferon

Previous results have demonstrated that nonspecific protective immunity against lethal Francisella tularensis live vaccine strain (LVS) or Listeria monocytogenes infection can be stimulated either by sublethal infection with bacteria or by treatment with bacterial DNA given 3 days before lethal challenge. Here we characterize the ability of purified lipopolysaccharide (LPS) from F. tularensis LVS to stimulate similar early protective immunity. Treatment of mice with surprisingly small amounts of LVS LPS resulted in very strong and long-lived protection against lethal LVS challenge within 2 to 3 days. Despite this strong protective response, LPS purified from F. tularensis LVS did not activate murine B cells for proliferation or polyclonal immunoglobulin secretion, nor did it activate murine splenocytes for secretion of interleukin-4 (IL-4), IL-6, IL-12, or gamma interferon (IFN-gamma). Immunization of mice with purified LVS LPS induced a weak specific anti-LPS immunoglobulin M (IgM) response and very little IgG; however, infection of mice with LVS bacteria resulted in vigorous IgM and IgG, particularly IgG2a, anti-LPS antibody responses. Studies using various immunodeficient mouse strains, including LPS-hyporesponsive C3H/HeJ mice, muMT(-) (B-cell-deficient) knockout mice, and IFN-gamma-deficient mice, demonstrated that the mechanism of protection does not involve recognition through the Lps(n) gene product; nonetheless, protection was dependent on B cells as well as IFN-gamma.     

Modulation of Murine Lymphocyte Mitogen Responses by Glycerol-Teichoic Acid

Glycerol-teichoic acid (GTA) showed a modulatory effect on the in vitro response of murine splenocytes to the mitogens concanavalin A (Con A) and lipopolysaccharide (LPS) as measured by incorporation of ³H-thymidine. GTA inhibited the response to Con A when added prior to addition of the mitogen, while addition 24 hr after had no significant effect on the response. The degree of suppression was dose dependent in a range from 0.1-5μg GTA/culture. The spleen cell response to LPS was enhanced by GTA when added prior to the mitogen. Peak enhancement occurred at 1-2 μgGTA/culture, depending on the time of addition. GTA added 24 hr after LPS produced no significant effect on mitogenesis. Addition of GTA alone to spleen cell cultures produced a slight suppression of DNA synthesis and was toxic at 10 μg/culture if incubated at least 66 hr. GTA is bound to murine spleen cells as indicated by decreased passive hemagglutination inhibition activity of culture supernates.     

Rheumatoid Synovial Fluid Reconstitutes the B-Cell Defect in CBA/N Mice

Synovial fluid from patients with rheumatoid arthritis (RA-SF) contains a biological activity which can replace T cells for activation of antibody secretion in human blood lymphoid cells and which can also induce the selective differentiation of IgG2b-secreting cells in lipopolysaccharide (LPS)-pre-activated mouse spleen cells. The B-cell activity of this factor was studied in CBA/N mice which have an X-linked B-cell immunodeficiency which manifests itself as a defective humoral response to certain thymus-independent antigens (TI-2). RA-SF has now been shown to reconstitute partly the B-cell deficiency in CBA/N splenic B cells in vitro. Addition of RA-SF to LPS-pretreated cell cultures results in IgG2b secretion in CBA/N spleen cells as well. In contrast to cells from normal CBA mice, cells from CBA/N mice cannot respond to interleukin 4 (IL-4) after addition of LPS with production of IgG1 antibodies in vitro. However, the addition of RA-SF completely restores a normal IL-4-induced IgG1 response. No other biologically active factors have been shown to allow the production of IgG antibody producing cells in CBA/N splenic B cells. It is postulated that the xid immunodeficiency could be the result of a deficient production of a biological activity which is abundant in RA-SF.