Joining of V kappa to J kappa gene segments in a retroviral vector introduced into lymphoid cells

V kappa to J kappa recombination occurred within a DNA construct introduced into cells in the form of a defective retrovirus. Analysis of one recombinant demonstrated that V kappa-J kappa joining can occur via inversion with a net loss of a few base pairs.     

Variability and repertoire size of T-cell receptor V alpha gene segments

The immune system of higher organisms is composed largely of two distinct cell types, B lymphocytes and T lymphocytes, each of which is independently capable of recognizing an enormous number of distinct entities through their antigen receptors; surface immunoglobulin in the case of the former, and the T-cell receptor (TCR) in the case of the latter. In both cell types, the genes encoding the antigen receptors consist of multiple gene segments which recombine during maturation to produce many possible peptides. One striking difference between B- and T-cell recognition that has not yet been resolved by the structural data is the fact that T cells generally require a major histocompatibility determinant together with an antigen whereas, in most cases, antibodies recognize antigen alone. Recently, we and others have found that a series of TCR V beta gene sequences show conservation of many of the same residues that are conserved between heavy- and light-chain immunoglobulin V regions, and these V beta sequences are predicted to have an immunoglobulin-like secondary structure. To extend these studies, we have isolated and sequenced eight additional alpha-chain complementary cDNA clones and compared them with published sequences. Analyses of these sequences, reported here, indicate that V alpha regions have many of the characteristics of V beta gene segments but differ in that they almost always occur as cross-hybridizing gene families. We conclude that there may be very different selective pressures operating on V alpha and V beta sequences and that the V alpha repertoire may be considerably larger than that of V beta.     

The murine T-cell receptor uses a limited repertoire of expressed V beta gene segments

Only 10 different V beta gene segments were found when the sequences of 15 variable (V beta) genes of the mouse T-cell receptor were examined. From this analysis we calculate that the total number of expressed V beta gene segments may be 21 or fewer, which makes the expressed germline V beta repertoire much smaller than that of immunoglobulin heavy-chain or light-chain genes. We suggest that beta-chain somatic diversification is concentrated at the V beta-D beta-J beta junctions.     

Somatic generation of antibody diversity

In the genome of a germ-line cell, the genetic information for an immunoglobulin polypeptide chain is contained in multiple gene segments scattered along a chromosome. During the development of bone marrow-derived lymphocytes, these gene segments are assembled by recombination which leads to the formation of a complete gene. In addition, mutations are somatically introduced at a high rate into the amino-terminal region. Both somatic recombination and mutation contribute greatly to an increase in the diversity of antibody synthesized by a single organism.     

人类抗体重排机制的起源

 重组激活基因（RAG）蛋白介导的抗体重排是脊椎动物适应性免疫系统的核心,抗体重排机制的起源一直是免疫学研究的热点。本研究以有活化石之称的文昌鱼为对象,对多个文昌鱼基因组草图进行深度信息学分析,发现了一个全新DNA转座子ProtoRAG。进一步功能研究表明,ProtoRAG编码的蛋白能够介导自身的转座和宿主DNA的重排,其作用机制与人类抗体蛋白介导的抗体重排机制基本一致。因此,ProtoRAG就是研究人员长期搜寻的祖先RAG转座子的“分子活化石”,该发现为诺贝尔生理学或医学奖获得者利根川进提出的“抗体重排机制转座子起源”假说提供了最有力和最直接的证据。     

Contribution of immunoglobulin heavy-chain variable-region genes to antibody diversity

A mouse cloned cDNA probe containing a variable (V) region belonging to the VHIII subgroup has been used in filter hybridisations to estimate the number of heavy-chain V-genes in this subgroup of mouse and human DNA. There seem to be about 10 and 20 VH-genes hybridising to this probe in mouse and human DNA, respectively. Studies of cross-hybridisation of the related VK-genes from MOPC21 and MPC11 myelomas indicate that the experiments detect all members of the VHIII subgroup.     

The structure, rearrangement and expression of D beta gene segments of the murine T-cell antigen receptor

It has been postulated that the variable region of the beta-polypeptide of the murine T-cell antigen receptor is encoded by three distinct germ-line gene segments--variable (V beta), diversity (D beta) and joining (J beta)--that are rearranged to generate a V beta gene. Germ-line V beta and J beta gene segments have been isolated previously. Here we report the isolation and characterization of two germ-line D beta gene segments that have recognition signals for DNA rearrangement strikingly similar to those found in the three immunoglobulin gene families and in V beta and J beta gene segments. The D beta and J beta segments can join in the absence of V beta gene segment rearrangement and these rearranged sequences are transcribed in some T cells.     

Chance, necessity and antibody gene dynamics

Early in their development B lymphocytes commit themselves to the expression of only one immunoglobulin light-chain gene and only one heavy-chain gene out of the large numbers of available loci. Here I shall present the view that the initial selection of loci for expression is made by chance, whereas the exclusion of other loci from expression is a necessity imposed by the physiology of lymphocyte development.     

加入WTO对山东省农业的影响及对策

我国加入WTO后对山东省的农业将会产生重大影响，我们应分清有利因素和不利因素，采取切实可行的对策措施，确保山东农业持续发展。     

入世背景下的金融监管

加入WTO后，我国必须处理好强化金融监管与金融适度开放的关系，监管模式要由分业监管逐渐向混业监管过渡。借鉴国外的经验，在监管中，要特别注意金融机构业务经营的合规性，资本充足性，资产质量，流动性，赢利能力，管理水平的内部控制。     

新生儿成熟度对免疫球蛋白重链可变区基因重排多样性的影响

目的分析不同胎龄新生儿免疫球蛋白重链可变区(IgH)基因序列特征，探讨新生儿成熟度对其多样性的影响。方法10例极不成熟儿、12例不成熟儿和11例成熟儿的脐血淋巴细胞DNA被抽提，IgH基因被扩增、克隆和测序。结果极不成熟儿和不成熟儿优先使用V     

Preferential utilization of the most JH-proximal VH gene segments in pre-B-cell lines

The most JH-proximal VH gene segments are used highly preferentially to form VHDJH rearrangements in pre-B-cell lines. This result demonstrates that the rate at which immunoglobulin VH gene segments recombine is influenced by their chromosomal organization, and that the initial repertoire of VH genes expressed in pre-B cells is strikingly different from that seen in mature populations.     

基于MFC的联接紧固件设计软件的研究与开发

目前Pro/Engineer应用日益普及,企业为了满足自身特殊需求需对其进行二次开发。针对Pro/Engineer二次开发工具Pro/Toolkit开发对话框较困难,提出利用动态链接库实现在Pro/Engineer中调用MFC对话框。使用面向对象的数据库编程技术,以Microsoft开放式数据连接(ODBC)模型为基础,结合MicrosoftAccess数据库,开发出界面友好、交互性强的联接紧固件系统。     

Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9

Variable regions 1 and 2 (V1/V2) of human immunodeficiency virus-1 (HIV-1) gp120 envelope glycoprotein are critical for viral evasion of antibody neutralization, and are themselves protected by extraordinary sequence diversity and N-linked glycosylation. Human antibodies such as PG9 nonetheless engage V1/V2 and neutralize 80% of HIV-1 isolates. Here we report the structure of V1/V2 in complex with PG9. V1/V2 forms a four-stranded β-sheet domain, in which sequence diversity and glycosylation are largely segregated to strand-connecting loops. PG9 recognition involves electrostatic, sequence-independent and glycan interactions: the latter account for over half the interactive surface but are of sufficiently weak affinity to avoid autoreactivity. The structures of V1/V2-directed antibodies CH04 and PGT145 indicate that they share a common mode of glycan penetration by extended anionic loops. In addition to structurally defining V1/V2, the results thus identify a paradigm of antibody recognition for highly glycosylated antigens, which-with PG9-involves a site of vulnerability comprising just two glycans and a strand.