Research Topics
| vdj exonsSummarySummary: Exons that are created in vivo during LYMPHOCYTE maturation from the V, D, and J gene segments of immunoglobulin superfamily genes (e.g., the IMMUNOGLOBULIN HEAVY CHAIN GENES, or the T-CELL RECEPTOR BETA GENES or T-CELL RECEPTOR GAMMA GENES ) by the VDJ RECOMBINASE system. Top Publications
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Publications
- Giblin W, Chatterji M, Westfield G, Masud T, Theisen B, Cheng H, et al. Leaky severe combined immunodeficiency and aberrant DNA rearrangements due to a hypomorphic RAG1 mutation. Blood. 2009;113:2965-75 pubmed publisher..Thus, our study provides in vivo evidence that implicates aberrant RAG1/2 activity in lymphoid tumor development and premature immunosenescence...
- Verma S, Aitken R. Somatic hypermutation leads to diversification of the heavy chain immunoglobulin repertoire in cattle. Vet Immunol Immunopathol. 2012;145:14-22 pubmed publisher..These data are consistent with a process of IgH diversification driven predominantly by somatic hypermutation. ..
- Reardon C. TCRJ and BCRJ gene segments contain 5' D-segment sequences that contribute to repertoire diversity. Immunogenetics. 2009;61:673-87 pubmed publisher..Additionally, in some cases, TCR and BCR genes that utilize separate D segments also receive additional D-like contributions though the 5' ends of their J segments to add additional diversity to their CDR3 loops. ..
- Komori A, Xu Z, Wu X, Zan H, Casali P. Biased dA/dT somatic hypermutation as regulated by the heavy chain intronic iEmu enhancer and 3'Ealpha enhancers in human lymphoblastoid B cells. Mol Immunol. 2006;43:1817-26 pubmed..This model system will be useful to further address the role of other cis-regulating elements and recruited trans-acting factors in expressing the modalities of SHM. ..
- Scifo C, Mekaelian L, Munyazesa E, Schmitt Verhulst A, Guimezanes A. Selection of T-cell receptors with a recurrent CDR3? peptide-contact motif within the repertoire of alloreactive CD8(+) T cells. Eur J Immunol. 2011;41:2414-23 pubmed publisher..Thus, a CDR3? motif generated by a process akin to "convergent recombination" accounts for a sizable fraction of the alloreactive anti-K(b) TCR repertoire. ..
- Perlot T, Pawlitzky I, Manis J, Zarrin A, Brodeur P, Alt F. Analysis of mice lacking DNaseI hypersensitive sites at the 5' end of the IgH locus. PLoS ONE. 2010;5:e13992 pubmed publisher..We conclude that deletion of these DNaseI hypersensitive sites does not have an obvious impact on the IgH locus or B cell development. ..
- Bhattacharyya A, Jones J. Requirement for ubiquitin conjugation and 26S proteasome activity at an early stage in V(D)J recombination. Mol Immunol. 2010;47:1173-80 pubmed publisher..These data suggest that ubiquitin-dependent degradation is an early step in complex assembly or activation, and are consistent with our previous hypothesis that degradation of a negative regulator is required to trigger recombination. ..
- Marantidou F, Dagklis A, Stalika E, Korkolopoulou P, Korkolopoulou P, Saetta A, et al. Activation-induced cytidine deaminase splicing patterns in chronic lymphocytic leukemia. Blood Cells Mol Dis. 2010;44:262-7 pubmed publisher..mutated IgMD cases (p=0.05). These results attest to the biological heterogeneity of CLL and also indicate that AID splice variants may inhibit SHM in CLL cells of the unmutated subtype. ..
- Hu D, Zheng H, Liu H, Li M, Ren W, Liao W, et al. Immunoglobulin expression and its biological significance in cancer cells. Cell Mol Immunol. 2008;5:319-24 pubmed publisher..We reviewed the recent progress in the study of cancer-derived Ig, and also discussed its mechanisms and possible functions, trying to arouse interest and attention to those working in the field of immunology and oncology. ..
- Jasper P, Rhee K, Kalis S, Sethupathi P, Yam P, Zhai S, et al. B lymphocyte deficiency in IgH-transgenic rabbits. Eur J Immunol. 2007;37:2290-9 pubmed..These IgH-Tg rabbits should provide a useful model for studies of B cell development both in bone marrow and in GALT. ..
- Sundling C, Phad G, Douagi I, Navis M, Karlsson Hedestam G. Isolation of antibody V(D)J sequences from single cell sorted rhesus macaque B cells. J Immunol Methods. 2012;386:85-93 pubmed publisher..The use of these primers will facilitate future efforts to clone and express rhesus macaque MAbs for genetic, functional and structural analyses. ..
- Zhu X, Li C, Sun X, Mao Y, Li G, Liu X, et al. Immunoglobulin mRNA and protein expression in human oral epithelial tumor cells. Appl Immunohistochem Mol Morphol. 2008;16:232-8 pubmed publisher..These results support that the phenomenon of Ig could also be expressed in oral cavity epithelial tumor cells. ..
- Martin Jimenez P, Garcia Sanz R, Gonzalez D, Balanzategui A, Perez J, Caballero M, et al. Molecular characterization of complete and incomplete immunoglobulin heavy chain gene rearrangements in hairy cell leukemia. Clin Lymphoma Myeloma. 2007;7:573-9 pubmed
- Krangel M. Mechanics of T cell receptor gene rearrangement. Curr Opin Immunol. 2009;21:133-9 pubmed publisher..Together these influences may explain the ordered activation and inactivation of T cell receptor locus recombination events and the phenomenon of Tcrb allelic exclusion. ..
- Kumar S, Wuerffel R, Achour I, Lajoie B, Sen R, Dekker J, et al. Flexible ordering of antibody class switch and V(D)J joining during B-cell ontogeny. Genes Dev. 2013;27:2439-44 pubmed publisher..We demonstrate that in the BM, V(D)J joining and switching are interchangeably inducible, providing an explanation for the hyper-IgE phenotype of Omenn syndrome. ..
- Wright K, Murray D, Crispe N, Pierce R. Quantitative PCR for detection of the OT-1 transgene. BMC Immunol. 2005;6:20 pubmed
- Pannicke U, Hönig M, Schulze I, Rohr J, Heinz G, Braun S, et al. The most frequent DCLRE1C (ARTEMIS) mutations are based on homologous recombination events. Hum Mutat. 2010;31:197-207 pubmed publisher..Functional analyses on patients' fibroblasts demonstrated that the corresponding alleles carry null mutations of the DCLRE1C gene. ..
- Martin Arruti M, Irastorza I, de Prado E, Martin Sanchez E, Martin Guerrero I, Ballesteros J, et al. Chromosome instability in lymphocytes of children with coeliac disease. J Pediatr Gastroenterol Nutr. 2009;49:143-6 pubmed publisher..No significant differences were found. ..
- Li F, Eckhardt L. A role for the IgH intronic enhancer E mu in enforcing allelic exclusion. J Exp Med. 2009;206:153-67 pubmed publisher..These findings reveal both an important role for E mu in influencing the fate of newly arising B cells and a second checkpoint for allelic exclusion. ..
- Khor B, Mahowald G, Khor K, Sleckman B. Functional overlap in the cis-acting regulation of the V(D)J recombination at the TCRbeta locus. Mol Immunol. 2009;46:321-6 pubmed publisher..Our findings demonstrate that cis-acting elements that regulate transcription and accessibility of the TCRbeta locus may functionally overlap with RS sequences, which are known primarily to direct Rag-mediated cleavage. ..
- Rouaud P, Vincent Fabert C, Saintamand A, Fiancette R, Marquet M, Robert I, et al. The IgH 3' regulatory region controls somatic hypermutation in germinal center B cells. J Exp Med. 2013;210:1501-7 pubmed publisher..Beyond class switch recombination, the IgH 3'RR is a central element that controls heavy chain accessibility to activation-induced deaminase modifications including SHM. ..
- Dujka M, Puebla Osorio N, Tavana O, Sang M, Zhu C. ATM and p53 are essential in the cell-cycle containment of DNA breaks during V(D)J recombination in vivo. Oncogene. 2010;29:957-65 pubmed publisher..This study shows the dynamic multiple functions of ATM in maintaining genomic stability and preventing tumorigenesis in developing lymphocytes. ..
- Cedar H, Bergman Y. Epigenetics of haematopoietic cell development. Nat Rev Immunol. 2011;11:478-88 pubmed publisher..In this Review, we describe the epigenetic changes that mediate this complex differentiation process and try to understand the logic of the programming mechanism. ..
- Jiang N, Weinstein J, Penland L, White R, Fisher D, Quake S. Determinism and stochasticity during maturation of the zebrafish antibody repertoire. Proc Natl Acad Sci U S A. 2011;108:5348-53 pubmed publisher..These data provide a window into the mechanisms of VDJ recombination and diversity creation and allow us to better understand how the adaptive immune system achieves diversity. ..
- Chen Z, Li J, Xiao Y, Zhang J, Zhao Y, Liu Y, et al. Immunoglobulin G locus events in soft tissue sarcoma cell lines. PLoS ONE. 2011;6:e21276 pubmed publisher..Collectively, these results confirmed IgG expression in sarcoma cells, the mechanism of which is very similar to that regulating IgG expression in B lymphocytes...
- Uduman M, Shlomchik M, Vigneault F, Church G, Kleinstein S. Integrating B cell lineage information into statistical tests for detecting selection in Ig sequences. J Immunol. 2014;192:867-74 pubmed publisher..We anticipate that this approach will be especially useful in the analysis of large-scale Ig sequencing data sets generated by high-throughput sequencing technologies. ..
- Yin B, Savic V, Juntilla M, Bredemeyer A, Yang Iott K, Helmink B, et al. Histone H2AX stabilizes broken DNA strands to suppress chromosome breaks and translocations during V(D)J recombination. J Exp Med. 2009;206:2625-39 pubmed publisher..We propose that such H2AX-dependent mechanisms could function at additional chromosomal locations to facilitate the joining of DNA ends generated by other types of DSBs. ..
- Weinstein J, Jiang N, White R, Fisher D, Quake S. High-throughput sequencing of the zebrafish antibody repertoire. Science. 2009;324:807-10 pubmed publisher..This approach provides insight into the breadth of the expressed antibody repertoire and immunological diversity at the level of an individual organism. ..
- Weterings E, Chen D. The endless tale of non-homologous end-joining. Cell Res. 2008;18:114-24 pubmed publisher..In this review, all the known enzymes that play a role in the NHEJ process are discussed and a working model for the co-operation of these enzymes during DSB repair is presented. ..
- Martin Jimenez P, Garcia Sanz R, Balanzategui A, Alcoceba M, Ocio E, Sanchez M, et al. Molecular characterization of heavy chain immunoglobulin gene rearrangements in Waldenström's macroglobulinemia and IgM monoclonal gammopathy of undetermined significance. Haematologica. 2007;92:635-42 pubmed..There is evidence that WM cells are able to undergo CSR in vivo, a fact that was initially thought to be impossible in this disease. ..
- Lieber M, Yu K, Raghavan S. Roles of nonhomologous DNA end joining, V(D)J recombination, and class switch recombination in chromosomal translocations. DNA Repair (Amst). 2006;5:1234-45 pubmed
- Hesslein D, Yang S, Schatz D. Origins of peripheral B cells in IL-7 receptor-deficient mice. Mol Immunol. 2006;43:326-34 pubmed..We conclude that the majority of splenic B cells in IL-7Ralpha-deficient mice originate from the bone marrow and not the fetal liver. ..
- Grundy G, Yang W, Gellert M. Autoinhibition of DNA cleavage mediated by RAG1 and RAG2 is overcome by an epigenetic signal in V(D)J recombination. Proc Natl Acad Sci U S A. 2010;107:22487-92 pubmed publisher..Thus a negative regulatory function of the noncore regions of RAG1/2 limits the RAG endonuclease activity in the absence of an activating methylated histone tail bound to the complex. ..
- Schelonka R, Szymanska E, Vale A, Zhuang Y, Gartland G, Schroeder H. DH and JH usage in murine fetal liver mirrors that of human fetal liver. Immunogenetics. 2010;62:653-66 pubmed publisher..However, fetal liver usage of J(H)-proximal D(H)Q52 and D(H)-proximal J(H)2 was markedly greater than that of adult bone marrow. Thus, the early pattern of D(H) and J(H) usage in mouse feta liver mirrors that of human. ..
- Meeker N, Smith A, Frazer J, Bradley D, Rudner L, Love C, et al. Characterization of the zebrafish T cell receptor beta locus. Immunogenetics. 2010;62:23-9 pubmed publisher..This description of the zebrafish TCRbeta locus has the potential to enhance immunological research in zebrafish and further our understanding of mammalian TCR repertoire generation. ..
- Perlot T, Li G, Alt F. Antisense transcripts from immunoglobulin heavy-chain locus V(D)J and switch regions. Proc Natl Acad Sci U S A. 2008;105:3843-8 pubmed publisher..Steady-state levels of antisense transcripts appeared very low, and start sites potentially appeared heterogeneous. We discuss the potential implications of antisense IgH locus transcription for AID targeting or other processes. ..
- Geng L, Shi Z, Dong Q, Cai X, Zhang Y, Cao W, et al. Expression of SNC73, a transcript of the immunoglobulin alpha-1 gene, in human epithelial carcinomas. World J Gastroenterol. 2007;13:2305-11 pubmed
- Ma B, Osborn M, Avis S, Ouisse L, Menoret S, Anegon I, et al. Human antibody expression in transgenic rats: comparison of chimeric IgH loci with human VH, D and JH but bearing different rat C-gene regions. J Immunol Methods. 2013;400-401:78-86 pubmed publisher..Furthermore, exclusion of C? and its downstream interval region may assist recombination. Highly diverse IgG and immune responses similar to normal rats were identified in two strains carrying diverse and differently spaced C-genes. ..