B淋巴细胞发育及分化研究进展

近年来，Ｂ淋巴细胞发育分化研究进展迅速，干细胞及不同发育阶段细胞离体培养的成功及ＰＣＲ靶向基因失活、转基因（鼠）等技术的发展及应用极大地推动了该领域研究，使Ｂ细胞发育分化调节、Ｂ细胞抗原受体及其抗原识别、信息传导管理论得到修正、补充和完善，并带动了Ｂ系相关免疫疾病如自身免疫，免疫缺陷，Ｂ系恶性肿瘤的研究。     

B淋巴细胞发育及分化研究进展

近年来，Ｂ淋巴细胞发育分化研究进展迅速，干细胞及不同发育阶段细胞离体培养的成功及ＰＣＲ靶向基因失活、转基因（鼠）等技术的发展及应用极大地推动了该领域研究，使Ｂ细胞发育分化调节、Ｂ细胞抗原受体及其抗原识别、信息传导等理论得到修正、补充和完善，并带动了Ｂ系相关免疫疾病如自身免疫、免疫缺陷，Ｂ系恶性肿瘤的研究。     

CD40分子在B细胞发育分化中的作用

B淋巴细胞在胚肝及骨髓中生成并经过一定阶段的分化发育,再迁移至外周免疫器官(包括淋巴结、脾脏及扁桃体)作为成熟的sIgD sIgM B细胞,亦称幼稚B细胞;在抗原特异性免疫反应中,B细胞经一系列连锁事件而成为分泌Ig的浆细胞或记忆性B细胞,这些事件包括特异性抗原识别、激活、扩增、体细胞突变、同种型转换和分化等。这些抗原依赖性事件发生在次级淋巴器官及非淋巴器官的不同区域,同时,B细胞必须与抗原以及T细胞、DCs等其他细胞发生接触及相互作用。这种相互作用是通过一系列不同的细胞膜表面分子及细胞因子来实现。其中最关键的膜分子之一是CD40分子。本文就B淋巴细胞的发育与分化过程中CD40分子可能的作用及其机制研究进展作一综述。     

CD40分子在B细胞发育分化中的作用

Ｂ淋巴细胞在胚肝及骨髓中生成并经过一定阶段的分化发育,再迁移至外周免疫器官作为成熟的ｓＩｇＤｓＩｇＭＢ细胞,亦称幼稚细胞;在抗原特异性免疫反应中,Ｂ细胞经一系列连锁事件而成为分泌Ｉｇ的浆细胞或记忆生Ｂ细胞, 事件包括特异性捩的识别、激活、扩增、体细胞突变、同种型转换和分化等。这些抗原依赖性事件发生在次级淋巴器官及非淋巴器官的不同区域,同时,Ｂ细胞必须与抗原以及Ｔ细胞、ＤＣｓ等其他细胞发生接触及相互     

RAG基因与T和B淋巴细胞分化发育

淋巴细胞抗原受体基因重排后，产生具有正常功能的抗原受体，对淋巴细胞正常分化发育至关重要，基因重排发生的机制至今仍不清楚。ＲＡＧ基因的发现及克隆化为阐明这一问题迈出了可喜的一步，本文综述了ＲＡＧ基因的结构，表达及与淋巴细胞分化发育的关系。     

B淋巴细胞发育的基因调控

B淋巴细胞通过形成抗原特异性免疫球蛋白在免疫过程中具有重要的作用。哺乳类动物B细胞分化最早部位是在胚胎早期的卵黄囊, 随后发生于胎肝, 在个体出生后进一步在骨髓中发育, 在外周淋巴器官中成熟。成熟B细胞定居于周围淋巴组织, 如淋巴结皮质浅层和脾的红髓及白髓的淋巴小结内。成熟的B细胞在抗原或者其他配体的刺激下形成分泌抗体的浆细胞, 执行体液免疫 [1]。对于B细胞发生, 基因调控有重要作用, 现对其发生过程以及涉及的几种主要调控基因综述如下。1　造血干细胞(hematopoieticstemcells)造血干细胞由处于静息状态的、自我更新…     

细胞因子与肠上皮内淋巴细胞的发育分化和生物学功能

肠上皮内淋巴细胞由多种Ｔ淋巴细胞亚群构成。部分亚群被认为是在胸腺外发育分化的。ＩＬ－７与ＩＬ－７Ｒ之间的信号传递对ＴＣＲγδ＾＋ｉＩＥＬ的发育分是必不可少的。ＩＬ－１５也可能对ｉＩＥＬ在胸腺外的发育和维持起重要的调节作用。ｉＩＥＬ能分泌多种细胞因子,在抗感染免疫和调节肠上皮细胞功能方面起重要作用。     

B淋巴细胞分化相关的基因调控

B淋巴细胞是免疫系统中的抗体产生细胞,是免疫系统的重要组成细胞.骨髓及胎肝中的多能造血干细胞(pluri-potent hematopoietic stem cells,PHSC)可以分化为具有向髓系以及淋巴系分化能力的多能前体细胞,它进一步分化为早期淋巴祖细胞.早期淋巴祖细胞在骨髓中分化为共同淋巴祖细胞.共同淋巴祖细胞能够分化产生B细胞、T细胞、自然杀伤细胞(natural killer cell,NK)以及树突状细胞(Den-dritic cells,DC).B淋巴细胞在骨髓中经历了顺序性分化:原B细胞(pro-B)→前B细胞(pre-B,包括pre-B Ⅰ和pre-BⅡ)→未成熟B细胞(immature B).     

线粒体功能在B细胞发育分化及活化中的作用

B细胞从骨髓起始发育,到外周器官成熟,是介导体液免疫的重要细胞。在抗原的刺激下,B细胞分化为浆细胞产生特异性抗体或分化为记忆B细胞。线粒体是细胞的能量产生及代谢中心,负责为细胞提供充足的能量。当线粒体功能受损时,会影响其能量供应,从而改变细胞的命运;而细胞的不同状态也会影响线粒体的功能。近年研究显示,线粒体功能在B细胞的发育和活化中起着重要作用,以适应细胞整个周期中遇到的表型和环境变化。本文主要综述了线粒体功能在B细胞发育、分化及活化过程中的作用,以及在B细胞的不同阶段、不同状态下发生的改变,为探究线粒体相关疾病的机制研究提供新思路,为B细胞相关疾病的治疗提供新的理论依据。     

T and B lymphocyte subpopulations and activation/differentiation markers in patients with selective IgA deficiency

Selective deficiency of immunoglobulin A (IgAD) and common variable immunodeficiency (CVID) are genetically closely related diseases, both of unknown pathogenesis. A plethora of abnormalities in lymphocyte subpopulations and expression of activation markers were repeatedly documented in CVID patients, while almost no data are available about lymphocyte subpopulations in IgAD patients. We determined basic lymphocyte subpopulations and those subpopulations that were reported to be abnormal in CVID patients (CD25, human leucocyte antigen (HLA)-DR CD45RA, CD45RO, CD27, CD28 and CD29 on both CD4(+) and CD8(+) cells, CD57 and CD38 on CD8(+) cells, CD21, CD27, IgM, IgD on B lymphocytes) in 85 patients with IgAD, 47 patients with CVID and in 65 healthy controls. Statistical analysis was performed by the Mann-Whitney U-test; significant P-values were determined by means of Bonferoni's correction. Our results showed an increase in the relative number of CD8(+) cells and a decrease in the absolute number of CD4(+) cells compared to healthy people, but similar abnormalities in CVID patients were much more expressed. IgAD patients had significantly decreased expression of HLA-DR and increased expression of CD25 on CD4(+) lymphocytes, also CD29 expression was decreased on CD8(+) cells, while other activation/differentiation markers on T cells (including the expression of CD45RA and CD45RO antigens) were not changed. There were no statistically significant abnormalities in B lymphocyte developmental stages in IgAD patients compared to healthy controls. Our observation showed that the majority of T and B lymphocyte subpopulation abnormalities described previously in CVID are not present in IgAD patients.     

Enhancement of terminal B lymphocyte differentiation in vitro by fibroblast-like stromal cells from human spleen

Stromal elements are major components of lymphoid tissues contributing to both tissue architecture and function. In this study we report on the phenotype and function of fibroblast-like stromal cells obtained from human spleen. These cells express high levels of CD44 and ICAM-1 and moderate levels of VLA-4, VCAM, CD40 and CD21. They fail to express endothelial, epithelial, lymphocyte and monocyte/macrophage markers. We show that these cells interact with B cell blasts induced in vitro by anti-CD40 and anti-μ stimulation. As a result of these interactions both IL-6 and IgG secretion into culture medium is increased. The enhanced secretion of IgG is partly inhibited by abolishing B cell blast-stromal cell contact or by anti-IL-6, anti-VCAM or anti-CD49d antibodies. Our studies also suggest that the ability of stromal cells to promote B cell survival is most likely the underlying mechanism of the enhanced immunoglobulin secretion. Comparison of stromal cells from different lymphoid and non-lymphoid organs revealed that bone marrow- and spleen-derived stromal cells are the most effective in promoting B cell blast differentiation.     

人可溶性B淋巴细胞刺激因子基因的克隆及在大肠杆菌中的表达

目的:钓取人B细胞刺激因子基因,构建其表达的大肠杆菌工程菌,并体外表达、纯化可溶性B细胞刺激因子方法:从人外周血单个核细胞(PBMC)中提取总RNA并逆转录得到cDNA,用PCR扩增目的基因,连接到原核生物表达载体pET-30a上。制备质粒后,酶切、进行菌落PCR及DN测序对其进行鉴定。然后转化大肠杆菌BL21(DE3)并表达对纯化的目的蛋白进行肽质量指纹分析、鉴定,并进一步做体外B细胞刺激试验。结果:RT-PCR钓取出可溶性B细胞刺激因子基因片段。DNA测序结果与报道序列完全一致。在IPTG诱导下,目的基因在工程菌中表达。利用镍金属螯合琼脂糖凝胶亲和层析柱分离。纯化目的蛋白的肽质量指纹图经Mascot搜索与B细胞刺激因子吻合。纯化的蛋白在体外可刺激B细胞增殖。结论:成功地克隆可溶性B细胞刺激因子基因,表达的纯化目的蛋白是具有生物学活性的B细胞刺激因子。     

B lymphocyte life span,rate of division and differentiation are regulated by total cell number

I analyzed how B cell survival, the rate of B cell division and the rate of B cell activation may be affected in mice with different numbers of peripheral B cells. For this purpose, I created bone marrow (BM) chimeras with different BM B cell production; I analyzed peripheral B cell dynamics in these animals and studied the fate of carboxyfluorescein succinimidyl ester-labeled lymph node B cells transferred into these mice. I found that in lymphopenic mice, B cell life span is shortened and the rates of terminal B cell differentiation and cell death increased. As a consequence, I did not observe accumulation of B cells in mice with reduced but constant B-cell-poiesis. These results suggest that peripheral B cell survival relies not only on the number of competitors, as previously shown, but also on the rate of throughput of cells in a particular compartment.     

Retinoic acid, neoplasia, differentiation and development

Retinoic acid has pronounced effects on cultures of neoplastic cells. These have attracted the attention of pathologists, but it is important to note that much of the critical data about retinoic acid has been obtained from the current extension of our knowledge in the field of development. Some of these changes are reviewed here.     

rhsBLyS对B淋巴细胞增殖的影响

目的测定可溶性重组人B淋巴细胞刺激因子(rhsBLyS)对B细胞的促增殖活性。方法通过FluroBeadsB荧光磁珠法体外分离并培养人B淋巴细胞,以CD20的特异性抗体标记之,借助流式细胞术检测。结果rhsBLyS非融合蛋白在引发剂AntiIgM的协同作用下表现出显著刺激B淋巴细胞增殖的活性。结论流式细胞术检测简便高效,在验证样品活性的同时为进一步开展工作奠定了基础。     

B淋巴细胞吞噬功能研究进展

以往的观点认为只有巨噬细胞、单核细胞、粒细胞和树突状细胞是专职的吞噬细胞,而B细胞作为免疫系统的抗体产生细胞,虽然能够产生特异的免疫球蛋白与抗原结合,却不具备吞噬能力。但最近的研究指出硬骨鱼类（彩虹鳟鱼）和两栖类（爪蟾）的B细胞可以吞噬颗粒抗原,首次揭示了进化上较为原始的B细胞同样具有吞噬能力。众多研究提示哺乳动物B-1 B细胞很可能具有吞噬能力。     

B/T淋巴细胞间抑制信号研究进展

B7-CD28家族共刺激信号分子在T淋巴细胞激活、抑制机体耐受及产生理想的T细胞免疫应答等方面起着关键作用。B7-CD28家族共信号分子已经被集中的研究,并且引起免疫调控领域充分的重视。CD80/CD86/CD28/CTLA-4经典途径的新功能的发现以及这一家族包括B7-H1/B7-DC/PD-1,B7-H2/ICOS,B7-H4和BTLA的新途径的确定,都拓宽了我们对T细胞介导的免疫应答和免疫耐受调控的理解。本文就CTLA-4、PD-1和BTLA对T细胞应答的负性调节以及在维持外周耐受中起作用的研究进展作一综述。     

脐血B淋巴细胞的免疫表型及临床意义

目的分析脐血 B淋巴细胞 ( B细胞 )的免疫表型及其临床意义。方法直接免疫荧光标记 ,流式细胞仪检测并对比研究 2 6例正常足月儿脐血和 15例正常成人外周血 B细胞相关表型表达。结果足月儿脐血中成熟 B细胞表型 CD19+ ,CD2 0 + CD19+ ,CD2 2 + CD19+ ,CD2 3 + CD19+ ,CD4 0 + CD19+ 的表达以及不成熟 B细胞表型 CD10 + CD19+ ,CD5 + CD19+ 的表达 ,除 CD2 3 + CD19+ 和 CD4 0 + CD19+ 外 ,均比正常人外周血高 ( P<0 .0 5 ) ,并且无性别之间差异 ( P>0 .0 5 )。结论与成人外周血比较脐血 B淋巴细胞相对不成熟