Base de dados : MEDLINE
Pesquisa : G05.344.401 [Categoria DeCS]
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[PMID]:28628091
[Au] Autor:Dolezal E; Infantino S; Drepper F; Börsig T; Singh A; Wossning T; Fiala GJ; Minguet S; Warscheid B; Tarlinton DM; Jumaa H; Medgyesi D; Reth M
[Ad] Endereço:Department for Molecular Immunology, Faculty of Biology, Albert-Ludwigs University of Freiburg, Freiburg, Germany.
[Ti] Título:The BTG2-PRMT1 module limits pre-B cell expansion by regulating the CDK4-Cyclin-D3 complex.
[So] Source:Nat Immunol;18(8):911-920, 2017 Aug.
[Is] ISSN:1529-2916
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Developing pre-B cells in the bone marrow alternate between proliferation and differentiation phases. We found that protein arginine methyl transferase 1 (PRMT1) and B cell translocation gene 2 (BTG2) are critical components of the pre-B cell differentiation program. The BTG2-PRMT1 module induced a cell-cycle arrest of pre-B cells that was accompanied by re-expression of Rag1 and Rag2 and the onset of immunoglobulin light chain gene rearrangements. We found that PRMT1 methylated cyclin-dependent kinase 4 (CDK4), thereby preventing the formation of a CDK4-Cyclin-D3 complex and cell cycle progression. Moreover, BTG2 in concert with PRMT1 efficiently blocked the proliferation of BCR-ABL1-transformed pre-B cells in vitro and in vivo. Our results identify a key molecular mechanism by which the BTG2-PRMT1 module regulates pre-B cell differentiation and inhibits pre-B cell leukemogenesis.
[Mh] Termos MeSH primário: Proliferação Celular/genética
Ciclina D3/metabolismo
Quinase 4 Dependente de Ciclina/metabolismo
Proteínas Imediatamente Precoces/genética
Linfopoese/genética
Células Precursoras de Linfócitos B/metabolismo
Proteína-Arginina N-Metiltransferases/genética
Proteínas Supressoras de Tumor/genética
[Mh] Termos MeSH secundário: Animais
Pontos de Checagem do Ciclo Celular
Diferenciação Celular/genética
Proteínas de Ligação a DNA/genética
Proteínas de Ligação a DNA/metabolismo
Citometria de Fluxo
Técnicas de Silenciamento de Genes
Rearranjo Gênico do Linfócito B/genética
Genes abl/genética
Proteínas de Homeodomínio/genética
Proteínas de Homeodomínio/metabolismo
Proteínas Imediatamente Precoces/metabolismo
Cadeias Leves de Imunoglobulina/genética
Espectrometria de Massas
Camundongos
Células Precursoras de Linfócitos B/citologia
Proteína-Arginina N-Metiltransferases/metabolismo
RNA Interferente Pequeno
Reação em Cadeia da Polimerase em Tempo Real
Proteínas Supressoras de Tumor/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Btg2 protein, mouse); 0 (Ccnd3 protein, mouse); 0 (Cyclin D3); 0 (DNA-Binding Proteins); 0 (Homeodomain Proteins); 0 (Immediate-Early Proteins); 0 (Immunoglobulin Light Chains); 0 (RNA, Small Interfering); 0 (Rag2 protein, mouse); 0 (Tumor Suppressor Proteins); 128559-51-3 (RAG-1 protein); EC 2.1.1.319 (Prmt1 protein, mouse); EC 2.1.1.319 (Protein-Arginine N-Methyltransferases); EC 2.7.11.22 (Cdk4 protein, mouse); EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170911
[Lr] Data última revisão:
170911
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170620
[St] Status:MEDLINE
[do] DOI:10.1038/ni.3774


  2 / 1547 MEDLINE  
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[PMID]:28502113
[Au] Autor:Dong Y; Wu C; Zhao X; Zhang P; Zhang H; Zheng M; Li S; Jiao J; Yu X; Lv Z; Ji Y
[Ad] Endereço:Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Centre, Xi'an, Shaanxi, China.
[Ti] Título:Epigenetic modifications of the V region after DJ recombination in Pro-B cells.
[So] Source:Immunology;152(2):218-231, 2017 Oct.
[Is] ISSN:1365-2567
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The variable region of murine immunoglobulin heavy chain (Igh) is assembled by sequential D -J and V -DJ recombination. The accessibility of the Igh locus determines the order of rearrangement. Because of the large number of V genes and the lack of a suitable model, the epigenetic modifications of V genes after DJ recombination have not previously been characterized. Here, we employed two v-Abl pro-B cell lines, in which the Igh locus is in germline and DJ -recombined configurations, respectively. The DJ junction displays the characteristics of a recombination centre, such as high levels of activation-associated histone modifications and recombination-activating gene protein (RAG) binding in DJ -rearranged pro-B cells, which extend the recombination centre model proposed for the germline Igh locus. The different domains of the V region have distinct epigenetic characteristics after DJ recombination. Distal V genes have higher levels of active histone modifications, germline transcription and Pax5 binding, and good quality recombination signal sequences. Proximal V genes are relatively close to the DJ recombination centre, which partially compensates for the low levels of the above active epigenetic modifications. DJ recombination centre might serve as a cis-acting element to regulate the accessibility of the V region. Furthermore, we demonstrate that RAG weakly binds to functional V genes, which is the first detailed assessment of RAG dynamic binding to V genes. We provide a way for V -DJ recombination in which the V gene is brought into close proximity with the DJ recombination centre for RAG binding by a Pax5-dependent chromosomal compaction event, and held in this position for subsequent cleavage and V -DJ joining.
[Mh] Termos MeSH primário: Epigênese Genética
Rearranjo Gênico do Linfócito B
Genes de Cadeia Pesada de Imunoglobulina
Região Variável de Imunoglobulina/genética
Células Precursoras de Linfócitos B/imunologia
[Mh] Termos MeSH secundário: Acetilação
Animais
Linhagem Celular Transformada
Imunoprecipitação da Cromatina
Proteínas de Ligação a DNA/imunologia
Proteínas de Ligação a DNA/metabolismo
Genes abl
Células HEK293
Histonas/metabolismo
Proteínas de Homeodomínio/imunologia
Proteínas de Homeodomínio/metabolismo
Seres Humanos
Região de Junção de Imunoglobulinas/genética
Região de Junção de Imunoglobulinas/imunologia
Região Variável de Imunoglobulina/imunologia
Região Variável de Imunoglobulina/metabolismo
Metilação
Camundongos
Camundongos Endogâmicos C57BL
Fator de Transcrição PAX5/genética
Fator de Transcrição PAX5/metabolismo
Células Precursoras de Linfócitos B/metabolismo
Ligação Proteica
Processamento de Proteína Pós-Traducional
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA-Binding Proteins); 0 (Histones); 0 (Homeodomain Proteins); 0 (Immunoglobulin Joining Region); 0 (Immunoglobulin Variable Region); 0 (PAX5 Transcription Factor); 0 (Pax5 protein, mouse); 0 (Rag2 protein, mouse); 128559-51-3 (RAG-1 protein)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170515
[St] Status:MEDLINE
[do] DOI:10.1111/imm.12758


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[PMID]:28438896
[Au] Autor:Longo NS; Rogosch T; Zemlin M; Zouali M; Lipsky PE
[Ad] Endereço:Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
[Ti] Título:Mechanisms That Shape Human Antibody Repertoire Development in Mice Transgenic for Human Ig H and L Chain Loci.
[So] Source:J Immunol;198(10):3963-3977, 2017 May 15.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:To determine the impact of the milieu on the development of the human B cell repertoire, we carried out a comprehensive analysis of productive and nonproductive Ig gene rearrangements from transgenic mice engineered to express single copies of the unrearranged human H chain and L chain Ig gene loci. By examining the nonproductive repertoire as an indication of the immediate product of the rearrangement machinery without an impact of selection, we discovered that the distribution of human rearrangements arising in the mouse was generally comparable to that seen in humans. However, differences between the distribution of nonproductive and productive rearrangements that reflect the impact of selection suggested species-specific selection played a role in shaping the respective repertoires. Although expression of some VH genes was similar in mouse and human (IGHV3-23, IGHV3-30, and IGHV4-59), other genes behaved differently (IGHV3-33, IGHV3-48, IGHV4-31, IGHV4-34, and IGHV1-18). Gene selection differences were also noted in L chains. Notably, nonproductive human VH rearrangements in the transgenic mice expressed shorter CDRH3 with less N addition. Even the CDRH3s in the productive rearrangements were shorter in length than those of the normal human productive repertoire. Amino acids in the CDRH3s in both species showed positive selection of tyrosines and glycines, and negative selection of leucines. The data indicate that the environment in which B cells develop can affect the expressed Ig repertoire by exerting influences on the distribution of expressed VH and VL genes and by influencing the amino acid composition of the Ag binding site.
[Mh] Termos MeSH primário: Linfócitos B/imunologia
Rearranjo Gênico de Cadeia Pesada de Linfócito B
Rearranjo Gênico do Linfócito B
Genes de Imunoglobulinas
Cadeias Pesadas de Imunoglobulinas/genética
Região Variável de Imunoglobulina/genética
[Mh] Termos MeSH secundário: Aminoácidos/análise
Animais
Animais Geneticamente Modificados
Genes de Cadeia Pesada de Imunoglobulina
Seres Humanos
Cadeias Pesadas de Imunoglobulinas/química
Cadeias Pesadas de Imunoglobulinas/imunologia
Imunoglobulina M
Região Variável de Imunoglobulina/química
Região Variável de Imunoglobulina/imunologia
Camundongos
Família Multigênica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids); 0 (Immunoglobulin Heavy Chains); 0 (Immunoglobulin M); 0 (Immunoglobulin Variable Region)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170426
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1700133


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[PMID]:28419441
[Au] Autor:Theunissen PMJ; Sedek L; De Haas V; Szczepanski T; Van Der Sluijs A; Mejstrikova E; Nováková M; Kalina T; Lecrevisse Q; Orfao A; Lankester AC; van Dongen JJM; Van Der Velden VHJ; EuroFlow Consortium
[Ad] Endereço:Department of Immunology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, the Netherlands.
[Ti] Título:Detailed immunophenotyping of B-cell precursors in regenerating bone marrow of acute lymphoblastic leukaemia patients: implications for minimal residual disease detection.
[So] Source:Br J Haematol;178(2):257-266, 2017 Jul.
[Is] ISSN:1365-2141
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Flow cytometric detection of minimal residual disease (MRD) in children with B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) requires immunophenotypic discrimination between residual leukaemic cells and B-cell precursors (BCPs) which regenerate during therapy intervals. In this study, EuroFlow-based 8-colour flow cytometry and innovative analysis tools were used to first characterize the immunophenotypic maturation of normal BCPs in bone marrow (BM) from healthy children, resulting in a continuous multiparametric pathway including transition stages. This pathway was subsequently used as a reference to characterize the immunophenotypic maturation of regenerating BCPs in BM from children treated for BCP-ALL. We identified pre-B-I cells that expressed low or dim CD34 levels, in contrast to the classical CD34 pre-B-I cell immunophenotype. These CD34 pre-B-I cells were relatively abundant in regenerating BM (11-85% within pre-B-I subset), while hardly present in healthy control BM (9-13% within pre-B-I subset; P = 0·0037). Furthermore, we showed that some of the BCP-ALL diagnosis immunophenotypes (23%) overlapped with CD34 pre-B-I cells. Our results indicate that newly identified CD34 pre-B-I cells can be mistaken for residual BCP-ALL cells, potentially resulting in false-positive MRD outcomes. Therefore, regenerating BM, in which CD34 pre-B-I cells are relatively abundant, should be used as reference frame in flow cytometric MRD measurements.
[Mh] Termos MeSH primário: Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico
Células Precursoras de Linfócitos B/fisiologia
[Mh] Termos MeSH secundário: Adolescente
Antígenos CD34/metabolismo
Medula Óssea/fisiologia
Diferenciação Celular/fisiologia
Pré-Escolar
Citometria de Fluxo
Rearranjo Gênico do Linfócito B/imunologia
Seres Humanos
Cadeias Pesadas de Imunoglobulinas/imunologia
Imunofenotipagem/métodos
Masculino
Neoplasia Residual
Leucemia-Linfoma Linfoblástico de Células Precursoras B/imunologia
Leucemia-Linfoma Linfoblástico de Células Precursoras B/fisiopatologia
Células Precursoras de Linfócitos B/imunologia
Células Precursoras de Linfócitos B/patologia
Regeneração
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD34); 0 (Immunoglobulin Heavy Chains)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170419
[St] Status:MEDLINE
[do] DOI:10.1111/bjh.14682


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[PMID]:28133793
[Au] Autor:Kepler TB; Wiehe K
[Ad] Endereço:Department of Microbiology, Boston University School of Medicine, Department of Mathematics and Statistics, Boston University, Boston, MA, USA.
[Ti] Título:Genetic and structural analyses of affinity maturation in the humoral response to HIV-1.
[So] Source:Immunol Rev;275(1):129-144, 2017 Jan.
[Is] ISSN:1600-065X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Most broadly neutralizing antibodies (BNAbs) elicited in response to HIV-1 infection are extraordinarily mutated. One goal of HIV-1 vaccine development is to induce antibodies that are similar to the most potent and broad BNAbs isolated from infected subjects. The most effective BNAbs have very high mutation frequencies, indicative of the long periods of continual activation necessary to acquire the BNAb phenotype through affinity maturation. Understanding the mutational patterns that define the maturation pathways in BNAb development is critical to vaccine design efforts to recapitulate through vaccination the successful routes to neutralization breadth and potency that have occurred in natural infection. Studying the mutational changes that occur during affinity maturation, however, requires accurate partitioning of sequence data into B-cell clones and identification of the starting point of a B-cell clonal lineage, the initial V(D)J rearrangement. Here, we describe the statistical framework we have used to perform these tasks. Through the recent advancement of these and similar computational methods, many HIV-1 ancestral antibodies have been inferred, synthesized and their structures determined. This has allowed, for the first time, the investigation of the structural mechanisms underlying the affinity maturation process in HIV-1 antibody development. Here, we review what has been learned from this atomic-level structural characterization of affinity maturation in HIV-1 antibodies and the implications for vaccine design.
[Mh] Termos MeSH primário: Vacinas contra a AIDS/imunologia
Afinidade de Anticorpos
Linfócitos B/imunologia
Rearranjo Gênico do Linfócito B
Infecções por HIV/imunologia
HIV-1/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Neutralizantes/metabolismo
Linfócitos B/virologia
Biologia Computacional
Anticorpos Anti-HIV/metabolismo
Seres Humanos
Ativação Linfocitária
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (AIDS Vaccines); 0 (Antibodies, Neutralizing); 0 (HIV Antibodies)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170814
[Lr] Data última revisão:
170814
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170131
[St] Status:MEDLINE
[do] DOI:10.1111/imr.12513


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[PMID]:27664314
[Au] Autor:Weidemann RR; Behrendt R; Schoedel KB; Müller W; Roers A; Gerbaulet A
[Ad] Endereço:Institute for Immunology, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany.
[Ti] Título:Constitutive Kit activity triggers B-cell acute lymphoblastic leukemia-like disease in mice.
[So] Source:Exp Hematol;45:45-55.e6, 2017 Jan.
[Is] ISSN:1873-2399
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and, in most cases, is of pro- or pre-B cell origin (B-ALL). The receptor tyrosine kinase KIT is expressed by hematopoietic stem and precursor cells. Gain-of-function mutations of KIT cause systemic mastocytosis, which is characterized by abnormal accumulations of mast cells. We previously reported a mouse model of mastocytosis based on conditional expression of a constitutively active Kit protein. Half of these animals developed leukemic disease of B-lineage origin. Herein, we report that this condition bears striking similarities to human B-ALL. The immuno-phenotype of the leukemic cells was compatible with a pro-B-cell origin, as was the finding of immunoglobulin heavy-chain gene rearrangements in all cases, whereas light-chain loci were mostly not rearranged. Leukemogenesis was independent of pre-B-cell receptor expression. Primary leukemic cells and permanent cell lines derived from these were serially transplantable and rapidly killed the recipients. In a few animals, the leukemia was of T-cell origin with abnormal CD4/8 double-positive T-cell precursors dominating in the circulation. In summary, we report a novel ALL mouse model that may prove useful for in vivo drug testing and identification of novel oncogenic mutations and principles.
[Mh] Termos MeSH primário: Transformação Celular Neoplásica/metabolismo
Leucemia-Linfoma Linfoblástico de Células Precursoras B/etiologia
Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo
Proteínas Proto-Oncogênicas c-kit/metabolismo
[Mh] Termos MeSH secundário: Animais
Linfócitos B/metabolismo
Linfócitos B/patologia
Biomarcadores
Transformação Celular Neoplásica/genética
Modelos Animais de Doenças
Ativação Enzimática
Rearranjo Gênico do Linfócito B
Loci Gênicos
Seres Humanos
Cadeias Pesadas de Imunoglobulinas/genética
Imunofenotipagem
Camundongos
Camundongos Transgênicos
Mutação
Fenótipo
Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidade
Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia
Células Precursoras de Linfócitos B/metabolismo
Células Precursoras de Linfócitos B/patologia
Proteínas Proto-Oncogênicas c-kit/genética
Receptores de Antígenos de Linfócitos B/metabolismo
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Immunoglobulin Heavy Chains); 0 (Receptors, Antigen, B-Cell); EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170904
[Lr] Data última revisão:
170904
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160925
[St] Status:MEDLINE


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[PMID]:27863542
[Au] Autor:Waugh EM; Gallagher A; Haining H; Johnston PEJ; Marchesi F; Jarrett RF; Morris JS
[Ad] Endereço:MRC-University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, 464 Bearsden Road, Glasgow, G61 1QH, UK. Electronic address: e.waugh.1@research.gla.ac.uk.
[Ti] Título:Optimisation and validation of a PCR for antigen receptor rearrangement (PARR) assay to detect clonality in canine lymphoid malignancies.
[So] Source:Vet Immunol Immunopathol;182:115-124, 2016 Dec.
[Is] ISSN:1873-2534
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:PCR for antigen receptor gene rearrangements (PARR) analysis is being increasingly used to assist diagnosis of canine lymphoma. In this study, PARR was carried out on consecutive samples received as part of routine diagnostic practice from 271 patients: 195 with lymphoid malignancies, 53 with reactive conditions and 23 with other neoplasms. Initially, published primer sets were used but later minor primer modifications were introduced and primers were rationalised to give a PARR panel that provides a good compromise between sensitivity and cost. Results were compared to diagnoses made by histology or cytology, coupled with immunophenotyping by flow cytometry or immunohistochemistry where possible. After exclusion of 11 poor quality samples, 230/260 (88%) gave a clear result with 162/163 (99%) of samples classified as clonal and 56/67 (84%) classified as polyclonal giving results concordant with the cytological/histological diagnosis. Among 30 samples with equivocal results, 21 had clonal peaks in a polyclonal background and nine showed little amplification. These were from patients with a range of neoplastic and non-neoplastic conditions emphasising the need to interpret such results carefully in concert with other diagnostic tests. The combination of primer sets used in this study resulted in a robust, highly specific and sensitive assay for detecting clonality.
[Mh] Termos MeSH primário: Doenças do Cão/genética
Doenças do Cão/imunologia
Rearranjo Gênico
Linfoma/veterinária
Reação em Cadeia da Polimerase/veterinária
Receptores de Antígenos/genética
[Mh] Termos MeSH secundário: Animais
Primers do DNA/genética
Doenças do Cão/diagnóstico
Cães
Feminino
Rearranjo Gênico do Linfócito B
Rearranjo Gênico do Linfócito T
Genótipo
Imunofenotipagem
Linfoma/genética
Linfoma/imunologia
Linfoma de Células B/genética
Linfoma de Células B/imunologia
Linfoma de Células B/veterinária
Linfoma de Células T/genética
Linfoma de Células T/imunologia
Linfoma de Células T/veterinária
Masculino
Reação em Cadeia da Polimerase/métodos
Reação em Cadeia da Polimerase/estatística & dados numéricos
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (DNA Primers); 0 (Receptors, Antigen)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161120
[St] Status:MEDLINE


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[PMID]:27828971
[Au] Autor:Walther S; Tietze M; Czerny CP; König S; Diesterbeck US
[Ad] Endereço:Department of Animal Sciences, Institute of Veterinary Medicine, Division of Microbiology and Animal Hygiene, Faculty of Agricultural Sciences, Georg-August University Goettingen, Goettingen, Germany.
[Ti] Título:Development of a Bioinformatics Framework for the Detection of Gene Conversion and the Analysis of Combinatorial Diversity in Immunoglobulin Heavy Chains in Four Cattle Breeds.
[So] Source:PLoS One;11(11):e0164567, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We have developed a new bioinformatics framework for the analysis of rearranged bovine heavy chain immunoglobulin (Ig) variable regions by combining and refining widely used alignment algorithms. This bioinformatics framework allowed us to investigate alignments of heavy chain framework regions (FRHs) and the separate alignments of FRHs and heavy chain complementarity determining regions (CDRHs) to determine their germline origin in the four cattle breeds Aubrac, German Black Pied, German Simmental, and Holstein Friesian. Now it is also possible to specifically analyze Ig heavy chains possessing exceptionally long CDR3Hs. In order to gain more insight into breed specific differences in Ig combinatorial diversity, somatic hypermutations and putative gene conversions of IgG, we compared the dominantly transcribed variable (IGHV), diversity (IGHD), and joining (IGHJ) segments and their recombination in the four cattle breeds. The analysis revealed the use of 15 different IGHV segments, 21 IGHD segments, and two IGHJ segments with significant different transcription levels within the breeds. Furthermore, there are preferred rearrangements within the three groups of CDR3H lengths. In the sequences of group 2 (CDR3H lengths (L) of 11-47 amino acid residues (aa)) a higher number of recombination was observed than in sequences of group 1 (L≤10 aa) and 3 (L≥48 aa). The combinatorial diversity of germline IGHV, IGHD, and IGHJ-segments revealed 162 rearrangements that were significantly different. The few preferably rearranged gene segments within group 3 CDR3H regions may indicate specialized antibodies because this length is unique in cattle. The most important finding of this study, which was enabled by using the bioinformatics framework, is the discovery of strong evidence for gene conversion as a rare event using pseudogenes fulfilling all definitions for this particular diversification mechanism.
[Mh] Termos MeSH primário: Diversidade de Anticorpos/genética
Bovinos/genética
Biologia Computacional/métodos
Conversão Gênica
Cadeias Pesadas de Imunoglobulinas/genética
[Mh] Termos MeSH secundário: Algoritmos
Animais
Diversidade de Anticorpos/imunologia
Cruzamento
Bovinos/classificação
Bovinos/imunologia
Regiões Determinantes de Complementaridade/genética
Regiões Determinantes de Complementaridade/imunologia
Expressão Gênica/genética
Expressão Gênica/imunologia
Rearranjo Gênico do Linfócito B/genética
Rearranjo Gênico do Linfócito B/imunologia
Cadeias Pesadas de Imunoglobulinas/imunologia
Região Variável de Imunoglobulina/genética
Região Variável de Imunoglobulina/imunologia
Análise de Sequência de DNA
Hipermutação Somática de Imunoglobulina/genética
Hipermutação Somática de Imunoglobulina/imunologia
Especificidade da Espécie
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Complementarity Determining Regions); 0 (Immunoglobulin Heavy Chains); 0 (Immunoglobulin Variable Region)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170703
[Lr] Data última revisão:
170703
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161110
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0164567


  9 / 1547 MEDLINE  
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[PMID]:27749910
[Au] Autor:Ralph DK; Matsen FA
[Ad] Endereço:Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
[Ti] Título:Likelihood-Based Inference of B Cell Clonal Families.
[So] Source:PLoS Comput Biol;12(10):e1005086, 2016 Oct.
[Is] ISSN:1553-7358
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The human immune system depends on a highly diverse collection of antibody-making B cells. B cell receptor sequence diversity is generated by a random recombination process called "rearrangement" forming progenitor B cells, then a Darwinian process of lineage diversification and selection called "affinity maturation." The resulting receptors can be sequenced in high throughput for research and diagnostics. Such a collection of sequences contains a mixture of various lineages, each of which may be quite numerous, or may consist of only a single member. As a step to understanding the process and result of this diversification, one may wish to reconstruct lineage membership, i.e. to cluster sampled sequences according to which came from the same rearrangement events. We call this clustering problem "clonal family inference." In this paper we describe and validate a likelihood-based framework for clonal family inference based on a multi-hidden Markov Model (multi-HMM) framework for B cell receptor sequences. We describe an agglomerative algorithm to find a maximum likelihood clustering, two approximate algorithms with various trade-offs of speed versus accuracy, and a third, fast algorithm for finding specific lineages. We show that under simulation these algorithms greatly improve upon existing clonal family inference methods, and that they also give significantly different clusters than previous methods when applied to two real data sets.
[Mh] Termos MeSH primário: Linfócitos B/imunologia
Sequenciamento de Nucleotídeos em Larga Escala/métodos
Modelos Genéticos
Receptores de Antígenos de Linfócitos B/genética
Receptores de Antígenos de Linfócitos B/imunologia
[Mh] Termos MeSH secundário: Células Clonais/imunologia
Simulação por Computador
Rearranjo Gênico do Linfócito B/genética
Rearranjo Gênico do Linfócito B/imunologia
Modelos Imunológicos
Modelos Estatísticos
Análise de Sequência de DNA
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, Antigen, B-Cell)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170516
[Lr] Data última revisão:
170516
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161018
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pcbi.1005086


  10 / 1547 MEDLINE  
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[PMID]:27665270
[Au] Autor:Li S; Liu W; Li Y; Zhao S; Liu C; Hu M; Yue W; Liu Y; Wang Y; Yang R; Xiang R; Liu F
[Ad] Endereço:Department of Immunology, School of Medicine, Nankai University, Tianjin 300071, China.
[Ti] Título:Contribution of secondary Igkappa rearrangement to primary immunoglobulin repertoire diversification.
[So] Source:Mol Immunol;78:193-206, 2016 Oct.
[Is] ISSN:1872-9142
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Abs reactive to DNA and DNA/histone complexes are a distinguished characteristic of primary immunoglobulin repertoires in autoimmune B6.MRL-Fas and MRL/MpJ-Fas mice. These mice are defective in Fas receptor, which is critical for the apoptosis of autoreactive B cells by an extrinsic pathway. In the present study, we explored the possibility that bone marrow small pre-B and immature B cells from adult B6.MRL-Fas mice and MRL/MpJ-Fas mice respectively, which contain autoreactive B-cell antigen receptors (BCR) and manifest autoimmune syndromes, exhibit enhanced receptor editing patterns. Indeed, FAS pre B and immature B cells were shown to possess more ongoing replacements of non-productive (nP) than productive (P) primary VκJκ rearrangements. Significantly, the P vs nP ratios of these replaced primary rearrangements were 1:2, thus indicating that κ light-chain production appears not to inhibit secondary rearrangements. In addition, we identified multiple atypical rearrangements, such as Vκ cRS (cryptic recombination signals) cleavages. These results suggest that the onset of light chain secondary rearrangements persists similarly as a non-selected mode and independent of BCR autoreactivity during certain developmental windows of bone marrow B cells in lupus-prone mice and control, and leads us to propose the function of secondary, de novo Igκ rearrangements to increase BCR diversity.
[Mh] Termos MeSH primário: Autoimunidade/imunologia
Rearranjo Gênico do Linfócito B/imunologia
Cadeias kappa de Imunoglobulina/imunologia
Receptores de Antígenos de Linfócitos B/imunologia
Tolerância a Antígenos Próprios/imunologia
[Mh] Termos MeSH secundário: Animais
Doenças Autoimunes/imunologia
Separação Celular
Citometria de Fluxo
Camundongos
Camundongos Endogâmicos MRL lpr
Reação em Cadeia da Polimerase
Células Precursoras de Linfócitos B/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Immunoglobulin kappa-Chains); 0 (Receptors, Antigen, B-Cell)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160926
[St] Status:MEDLINE



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