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Diversity of Antigen Receptors01:28

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Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
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Mismatch Repair01:20

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Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
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Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new...
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DNA replication is a well-evolved process that copies millions of base pairs with high fidelity during each cell division. Occasionally a wrong base or a long stretch of wrong bases may get added to the daughter strands. If the errors are left unchecked, cells might accumulate several mutations that might endanger their  survival. Therefore, the copying errors are checked and repaired at three levels.
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Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
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Video Experimental Relacionado

Updated: Aug 1, 2025

Analysis of Somatic Hypermutation in the JH4 intron of Germinal Center B cells from Mouse Peyer's Patches
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La característica del ADN de mesoscala en la secuencia codificadora de anticuerpos facilita la hipermutación somática

Yanyan Wang1, Senxin Zhang2, Xinrui Yang3

  • 1State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Shanghai Institute of Immunology, Department of Immunology and Microbiology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Cell
|April 25, 2023
PubMed
Resumen

La hipermutación somática (SHM) se centra en los genes de anticuerpos debido a la flexibilidad del ADN cerca de la enzima citidina desaminasa inducida por activación (AID). Esta flexibilidad guía las mutaciones, mejorando la diversidad de anticuerpos y ayudando a la investigación del linfoma.

Palabras clave:
AID (en inglés)maduración por afinidadRegión que determina la complementariedaddeaminasahipermutación somática

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Área de la Ciencia:

  • Inmunología
  • Biología molecular
  • La genética

Sus antecedentes:

  • La hipermutación somática (SHM) es crucial para la maduración de la afinidad de los anticuerpos.
  • La orientación precisa de SHM a las regiones determinantes de la complementariedad de anticuerpos (CDR) no se comprende completamente.
  • La desaminasa citidina inducida por activación (AID) inicia la SHM mediante la desaminación del ADN.

Objetivo del estudio:

  • Esclarecer el mecanismo que determina la especificidad de las mutaciones iniciadas por AID en los genes de anticuerpos.
  • Investigar el papel de la secuencia y la estructura del ADN en la dirección de la SHM.
  • Explorar las implicaciones para el descubrimiento de anticuerpos y la patogénesis del linfoma.

Principales métodos:

  • Ensayos in vitro de las desaminasas utilizando diferentes sustratos de ADN.
  • Análisis de las características de la secuencia de ADN a mesoescala que rodean los motivos de AID.
  • Análisis mutacional in vivo en modelos de ratón.
  • Análisis de conservación evolutiva de los patrones de SHM.

Principales resultados:

  • La flexibilidad del sustrato de ADN, dictada por las secuencias de mesoescala, rige la unión y desaminación de AID.
  • Las secuencias pirimidina-pirimidina mejoran la actividad de AID al interactuar con su superficie cargada.
  • La hipermutabilidad de la CDR puede imitarse in vitro y se conserva evolutivamente.
  • La alteración de las secuencias de mesoescala modifica la mutabilidad in vivo y promueve mutaciones en regiones específicas.

Conclusiones:

  • Las secuencias de genes de anticuerpos poseen características intrínsecas que dirigen la mutagenesis de AID a través de la flexibilidad del ADN.
  • Las propiedades de la secuencia de mesoscala juegan un papel crítico en la determinación de los patrones de SHM.
  • Los hallazgos ofrecen información sobre la ingeniería de anticuerpos, modelos animales humanizados y el desarrollo del linfoma.