Chromosomal locations of the murine T-cell receptor alpha-chain gene and the T-cell gamma gene

Two independent methods were used to identify the mouse chromosomes on which are located two families of immunoglobulin (Ig)-like genes that are rearranged and expressed in T lymphocytes. The genes coding for the alpha subunit of T-cell receptors are on chromosome 14 and the gamma genes, whose function is yet to be determined, are on chromosome 13. Since genes for the T-cell receptor beta chain were previously shown to be on mouse chromosome 6, all three of the Ig-like multigene families expressed and rearranged in T cells are located on different chromosomes, just as are the B-cell multigene families for the Ig heavy chain, and the Ig kappa and lambda light chains. The findings do not support earlier contentions that genes for T-cell receptors are linked to the Ig heavy chain locus (mouse chromosome 12) or to the major histocompatibility complex (mouse chromosome 17).     

Location of gene for beta subunit of human T-cell receptor at band 7q35, a region prone to rearrangements in T cells

The T-cell receptor is formed by two chains, alpha and beta, for which specific clones were recently obtained. In this report the gene for the beta chain of the human T-cell receptor was located on the long arm of chromosome 7, band q35, by means of in situ hybridization. This chromosome region in T cells is unusually prone to develop breaks in vivo, perhaps reflecting instability generated by somatic rearrangement of T-cell receptor genes during normal differentiation in this cell lineage.     

A novel mechanism of somatic rearrangement predicted by a human T-cell antigen receptor beta-chain complementary DNA

The T-cell antigen receptor is a cell surface molecule vital in mediating the cellular immune response. The arrangement and rearrangement of the gene segments encoding the beta-chain polypeptide of the receptor are similar to those of immunoglobulin gene segments. The two constant region genes of the human T-cell antigen receptor are 8 kilobases apart with a cluster of joining segments located 5' of each constant region gene. Although most beta-chain gene rearrangements involve the variable, diversity, and joining segments, analysis of a beta-chain complementary DNA clone suggests the occasional occurrence of another type of rearrangement.     

Immortalization of human T lymphocytes after transfection of Epstein-Barr virus DNA

Epstein-Barr virus (EBV), a ubiquitous human herpesvirus, has the ability to transform human B lymphocytes. No other cell type has been experimentally transformed by EBV, either by intact virions or naked viral DNA and subgenomic fragments. Two immortalized human T-lymphoblastoid cell lines have now been established by transfecting cord blood lymphocytes with purified B95-8 viral DNA enclosed in fusogenic Sendai virus envelopes (RSVE) and then exposing the cells to EBV from a P3HR-1 cell subclone. One of these lines, which has been fully characterized, is termed HBD-1. This line is positive for EBV DNA and expresses surface OKT11, OKT4, and Tac receptors, but not M-1, mu immunoglobulin chains, EBV receptors, or B-1 surface markers. The cells contain fully rearranged T-cell receptor genes and germline immunoglobulin genes. The karyotype of the cells is normal, they do not require interleukin-2 for growth, and do not contain human T-lymphotropic virus type I. However, the HBD-1 cells contain incomplete EBV genomes and express several EBV-determined antigens, including the early antigen type D, membrane antigens, but not EBV-determined nuclear antigen (EBNA). This association of the EBV genome with permanently growing hematopoietic cells of non B-cell lineage should prove useful in studies on the mechanism of EBV-mediated cell transformation.     

Common mechanism of chromosome inversion in B- and T-cell tumors: relevance to lymphoid development

An inversion of chromosome 14 present in the tumor cells of a patient with childhood acute lymphoblastic leukemia of B-cell lineage was shown to be the result of a site-specific recombination event between an immunoglobulin heavy-chain variable gene and the joining segment of a T-cell receptor alpha chain. This rearrangement resulted in the formation of a hybrid gene, part immunoglobulin and part T-cell receptor. Furthermore, this hybrid gene was transcribed into messenger RNA with a completely open reading frame. Thus, two loci felt to be normally activated at distinct and disparate points in lymphocyte development were unified and expressed in this tumor.     

鸡Igλ轻链基因克隆、序列分析及其在COS7细胞膜上的定位表达

为了研究鸡B细胞膜免疫球蛋白(mIg)的功能,深入了解鸡免疫系统抗体基因的特点,从鸡法氏囊B细胞cDNA中扩增出Igλ轻链基因,对其核苷酸序列和氨基酸序列进行了分析和比较。该基因cDNA全长873bp,编码含226个氨基酸的Igλ轻链,N-端21个氨基酸构成轻链信号肽,随后是2个Ig样结构域。运用融合PCR的方法将该基因与牛IgG Fc受体γRⅡ跨膜区序列嵌合形成重组跨膜分子,构建真核表达载体pcDNA-λR2T,转染COS7细胞,荧光抗体染色及流式细胞术检测到重组鸡Igλ轻链在细胞膜上的表达。所扩增的鸡Igλ轻链基因以及构建表达于细胞膜上的重组鸡Igλ轻链跨膜分子,为研究鸡免疫系统中的抗体轻链基因,探索Igλ轻链和B细胞膜免疫球蛋白的功能奠定技术基础。     

Human T-cell receptor alpha-chain genes: location on chromosome 14

The genes encoding the alpha chain of the human T-cell receptor have been mapped to chromosome 14, the chromosome on which the human immunoglobulin heavy chain locus resides. Thus, genes encoding two different classes of antigen receptor are present on the same chromosome. Furthermore, breaks involving chromosome 14 are frequently seen in tumors of T-cell origin. The potential relation of these chromosome abnormalities to alpha-chain genes is discussed.     

Depletion of conventional mature B cells and compromised specific antibody response in bovine immunoglobulin μ heavy-chain transgenic mice

In this study, we introduced the bovine immunoglobulin μ heavy-chain gene (the orphaned gene on BTA11) into mouse germline cells. Bovine IgM was highly expressed in selected transgenic lines, and it largely inhibited rearrangements of the endogenous immunoglobulin heavy chain (IgH) genes in these lines. The forced expression of bovine IgM resulted in reduced numbers of pro- and pre-B cells but increased the number of immature B cells in the transgenic mice. Bovine IgM-expressing B cells can migrate from the bone marrow to the spleen, but most of the cells are arrested at the T1 transitional B cell stage, leading to a significantly lower number of T2 transitional and mature B cells in the spleen. Although the serum concentrations of endogenous IgM and IgG in the transgenic mice were significantly decreased, the IgA levels were slightly increased compared to the WT mice. The bovine IgM level in the serum was only one-tenth to one-fifth of that of endogenous mouse IgM, suggesting that most of the serum immunoglobulin were contributed by endogenous IgH gene-expressing B cells. These transgenic mice also exhibited a lower frequency of unique complementarity determining region 3 (CDR3) sequences in their VH repertoire and Vκ repertoire but exhibited an increased frequency of unique CDR3 in their Vλ repertoire. Compared to the WT mice, the transgenic mice had a significantly higher percentage of mouse IgM-expressing B cells that expressed λ chains. Finally, we showed that the transgenic mice were deficient in a specific antibody response to antigen stimulation.     

The structure, function, and expression of interleukin-2 receptors on normal and malignant lymphocytes

Antigen or mitogen-induced activation of resting T cells induces the synthesis of interleukin-2 (IL-2) as well as the expression of specific cell surface receptors for this lymphokine. Failure of the production of either IL-2 or its receptor results in a failure of the T-cell immune response. The receptor is composed of a 33,000-dalton (251-amino acid) peptide precursor that is post-translationally glycosylated into the mature 55,000-dalton form. In contrast to resting T cells, human T-cell lymphotrophic virus I (HTLV-I)-associated adult T-cell leukemia cells constitutively express large numbers of IL-2 receptors. Because IL-2 receptors are present on the malignant T cells but not on normal resting cells, clinical trials have been initiated in which patients with adult T-cell leukemia are treated with a monoclonal antibody that binds to the IL-2 receptor.     

Contribution of receptor editing to the antibody repertoire

Receptor editing, clonal deletion, and anergy are the mechanisms by which B cells maintain tolerance to self antigens. To determine the extent to which receptor editing shapes the normal antibody repertoire, we generated an immunoglobulin kappa polymorphism that facilitates the detection of editing of immunoglobulin light chains in vivo. We found that B cells are targeted for editing during a 2-hour delay in development at the pre-BII cell stage, and that about 25% of all antibody molecules are produced by gene replacement. These results suggest that receptor editing represents a major force in shaping the antibody repertoire.     

Gene for alpha-chain of human T-cell receptor: location on chromosome 14 region involved in T-cell neoplasms

A human complementary DNA clone specific for the alpha-chain of the T-cell receptor and a panel of rodent X human somatic cell hybrids were used to map the alpha-chain gene to human chromosome 14 in a region proximal to the immunoglobulin heavy chain locus. Analysis by means of in situ hybridization of human metaphase chromosomes served to further localize the alpha-chain gene to region 14q11q12, which is consistently involved in translocations and inversions detectable in human T-cell leukemias and lymphomas. Thus, the locus for the alpha-chain T-cell receptor may participate in oncogene activation in T-cell tumors.     

Chromatin structure and de novo methylation of sperm DNA: implications for activation of the paternal genome

The chromatin structure characteristic of constitutively expressed genes, tissue-specific genes, and inactive genes is absent in chicken sperm chromatin. However, point sites of undermethylation in sperm DNA within constitutively expressed genes, but not within globin genes or an inactive gene, correspond to the location of regions of altered chromatin structure (hypersensitive sites) in somatic tissue and spermatogonial cells. A de novo methylation process whereby regions within and flanking these genes become methylated, but which excludes the methylation of sequences within hypersensitive sites, occurs between the spermatogonial stage and the first meiotic prophase. These undermethylated regions may play a role in the activation of the paternal genome during embryogenesis.