VDJ recombination articles within Nature Communications

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  • Article
    | Open Access

    Regulation of thymocyte development by RNA-binding proteins is not fully characterized. Here the authors show the RBP ARPP21 interacting with the Rag1 3’-UTR to promote Rag1 expression, TCR rearrangement and an increased diversity of the TCR repertoire and that ARPP21 is down regulated by TCR stimulation.

    • Meng Xu
    • , Taku Ito-Kureha
    •  & Vigo Heissmeyer

  • Article
    | Open Access

    Myelomagenesis progresses through well-defined pre-malignant states. Here, using single-cell RNA sequencing and T cell receptor repertoire analysis of bone marrow T cells in patients at different stages of myelomagenesis, the authors identify large clonotypic expansions characterized by the expression of multiple immune checkpoints.

    • Cirino Botta
    • , Cristina Perez
    •  & Bruno Paiva

  • Article
    | Open Access

    V gene recombination at the immunoglobulin heavy chain locus (Igh) is facilitated by extended loop extrusion. In this study, the authors find that, unlike Igh, the κ light chain locus does not involve extended loop extrusion but instead involves multiple, short-range loops for V gene combination.

    • Louisa Hill
    • , Gordana Wutz
    •  & Meinrad Busslinger

  • Article
    | Open Access

    Omicron strains of SARS-CoV-2 have displayed high transmissibility and immunological escape to antibody responses derived from natural infection and vaccination. Here the authors compare the antibody response to vaccination and natural infection, assessing neutralisation after vaccine doses and analyse the repertoire of such responses.

    • Emanuele Andreano
    • , Ida Paciello
    •  & Rino Rappuoli

  • Article
    | Open Access

    SARS-CoV-2 vaccines and infection induce antibody responses but the evolution of subsequent variants has resulted in the development of escape mutants. Here the authors characterise, at single cell level, the antibody response in donors after a third dose of SARS-CoV-2 mRNA vaccination and show difference in breadth, neutralisation and molecular signature according to the vaccination regimen used.

    • Emanuele Andreano
    • , Ida Paciello
    •  & Rino Rappuoli

  • Article
    | Open Access

    SHLD1, as a component of the Shieldin (SHLD) complex, mediates DNA repair via non-homologous end-joining (NHEJ), an essential process during lymphocyte development. Here the authors show that SHLD1 is actually dispensable for lymphocyte development and V(D)J recombination, but is essential for class-switching recombination in activated B cells.

    • Estelle Vincendeau
    • , Wenming Wei
    •  & Ludovic Deriano

  • Article
    | Open Access

    Lancelet expresses an ancestral RAG transposon, ProtoRAG, which predates human RAGgenes that are responsible for V(D)J recombination and adaptive immunity repertoire generation. Here the authors show that ProtoRAG is functionally regulated by a trans-acting factor, bbYY1, for tuning transposon activity and maintaining genome stability.

    • Song Liu
    • , Shaochun Yuan
    •  & Anlong Xu

  • Article
    | Open Access

    B cell development is tightly regulated in a stepwise manner to ensure proper generation of repertoire diversity via somatic gene rearrangements. Here, the authors show that a transcription factor, Erg, functions at the earliest stage to critically control two downstream factors, Ebf1 and Pax5, for modulating this gene rearrangement process.

    • Ashley P. Ng
    • , Hannah D. Coughlan
    •  & Warren S. Alexander

  • Article
    | Open Access

    B-1a B cells are innate-like cells with biased reactivity to bacteria and self-antigens. Here the authors show that reduced interleukin-7 in developing fetal liver-derived pro-B cells induces premature immunoglobulin κ rearrangement, alleviating the requirement for a pre-BCR selection stage and allowing the generation of autoreactive B1-a B cells.

    • Jason B. Wong
    • , Susannah L. Hewitt
    •  & Jane A. Skok

  • Article
    | Open Access

    The repertoire of adaptive immune receptor is generated by V(D)J recombination, somatic rearrangements of V, D and J gene segments, in the respective loci. Here the authors show that the deficiency of Setd2, a histone methyl transfer, impairs V(D)J recombination and induces severe developmental blocks in both T and B lineages.

    • Zhongzhong Ji
    • , Yaru Sheng
    •  & Helen He Zhu

  • Article
    | Open Access

    Adaptive immunity from both B and T cells critically controls the rejection or survival of transplanted organs. Here the authors show, by analyzing human B cell receptor repertoire in longitudinal studies of patients receiving kidney transplants, that repertoire diversity is positively associated with the incidence of kidney rejection.

    • Silvia Pineda
    • , Tara K. Sigdel
    •  & Minnie M. Sarwal

  • Article
    | Open Access

    Analysis of large-scale immune repertoire architecture remains a challenge. Here, the authors introduce an approach to construct similarity networks from high-throughput antibody repertoire sequencing data, and show that the networks are redundant, robust and reproducible across individuals.

    • Enkelejda Miho
    • , Rok Roškar
    •  & Sai T. Reddy

  • Article
    | Open Access

    For T cells, functional antigen receptors are selected in the thymus from a pre-selection repertoire by interaction with self MHCs. Here the authors show that specific, non-germline coded features located in the complementarity determining region 3 of the pre-selection antigen receptors are essential for the selection of MHC-restricted repertoire.

    • Jinghua Lu
    • , François Van Laethem
    •  & Peter D. Sun

  • Article
    | Open Access

    T cell receptors are generated by somatic gene recombination, and are normally selected against autoreactivity. Here the authors show that CD4 T cells from patients with autoimmune type 1 diabetes have shorter TCRβ sequences, broader repertoire diversity, and more repertoire sharing than those from healthy individuals.

    • Iria Gomez-Tourino
    • , Yogesh Kamra
    •  & Mark Peakman

  • Article
    | Open Access

    Longevity of antibody responses has been attributed to persistence of plasma cells in mice. Here the authors provide human data in support of this model by immunoglobulin sequencing bone marrow sections from two human donors over 6.5 years to show temporal stability of plasma cell clonotypes, but not other B cells.

    • Gabriel C. Wu
    • , Nai-Kong V. Cheung
    •  & Gregory C. Ippolito

  • Article
    | Open Access

    Antigen receptor diversity relies on careful DNA cleavage and repair. Here the authors identify a functional interplay between RAG2 and XLF during V(D)J recombination, revealing an important role for the RAG complex in repairing induced DNA double-strand breaks and maintaining genome integrity.

    • Chloé Lescale
    • , Vincent Abramowski
    •  & Ludovic Deriano

  • Article |

    Self-reactive B cells producing autoantibodies are associated with autoimmune conditions. Here, the authors show that in mice lacking the surrogate light chain, which normally assembles with antibody heavy chain to form a pre-B-cell receptor, the autoantibody-producing cells derive from germinal centres.

    • Ola Grimsholm
    • , Weicheng Ren
    •  & Inga-Lill Mårtensson

  • Article
    | Open Access

    B cells rearrange the immunoglobulin heavy chain genes to produce a functional B cell receptor, but how it is decided that one allele rearranges first is not clear. Here the authors provide evidence that in the majority of common lymphoid precursor clones, the two alleles have a similar probability of rearranging first.

    • Clara F. Alves-Pereira
    • , Raquel de Freitas
    •  & Vasco M. Barreto

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