Class switch recombination articles within Nature Communications

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  • Article
    | Open Access

    B cell activation and differentiation entails metabolic remodelling, involving differential utilisation of monocarboxylates such as L-lactate and pyruvate. Here authors show by B-cell-specific genomic deletion of monocarboxylate transporter 1 (MCT1) that the consequential scarcity of pyruvate results in decreased acetylation of Histone H3 at K27, leading to decreased AID transcription and deficient class switching to IgG.

    • Wenna Chi
    • , Na Kang
    •  & Ligong Chen

  • Article
    | Open Access

    Class switch recombination (CSR) is a process by which B cells switch their immunoglobulin isotype and develop pathogen-eliminating antibodies. Here, the authors show that a protein kinase DYRK1A is required for protection from viral infection through the regulation of CSR and effective clonal expansion.

    • Liat Stoler-Barak
    • , Ethan Harris
    •  & Ziv Shulman

  • 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

    IgD is expressed, predominantly together with IgM, via mRNA alternative splicing, but IgD class switch recombination (IgD CSR) has also been reported. Here the authors show, using Rad52-deficient mouse and human B cells, that IgD CSR is mediated by Rad52 through an alternative, microhomology-based end-joining pathway of DNA repair.

    • Yijiang Xu
    • , Hang Zhou
    •  & Paolo Casali

  • Article
    | Open Access

    Human memory B cells differentiate from naïve B cells and can express different immunoglobulin (Ig) isotypes resulted from class-switch recombination. Here the authors describe, using transcriptional and epigenetic data from human memory B cells and integrated multi-omics analyses, the differentiation regulation and trajectory of IgG+, IgA+ and IgD+ memory B cells.

    • Justin B. Moroney
    • , Anusha Vasudev
    •  & Paolo Casali

  • Article
    | Open Access

    REV7 has emerged as a critical regulator of DNA double-strand breaks repair. Here, the authors show that REV7 is crucial for both antibody class switch recombination and somatic hypermutation in activated B cells, in addition to their survival upon AID-deamination.

    • Dingpeng Yang
    • , Ying Sun
    •  & Fei-Long Meng

  • Article
    | Open Access

    Dietary fiber-derived short-chain fatty acids (SCFA) act as histone deacetylase (HDAC) inhibitors on Tregs and innate immune cells, promoting immune tolerance by altering gene expression. Here the authors show that SCFA HDAC inhibitor activity impacts B cell differentiation, antibody responses and antibody-driven autoimmunity.

    • Helia N. Sanchez
    • , Justin B. Moroney
    •  & Paolo Casali

  • Article
    | Open Access

    Activation-induced deaminase (AID) is important for inducing desirable mutations at the B cell receptor genes for effective antibody responses. Here the authors show that three key arginine residues of AID link AID-chromatin association with transcription elongation to license AID for specific mutagenesis in B cells.

    • Stephen P. Methot
    • , Ludivine C. Litzler
    •  & Javier M. Di Noia

  • Article
    | Open Access

    Class switch recombination (CSR) requires break and repair of immunoglobulin DNA. Here the authors show that the histone deubiquitinase Usp22 is involved in V(D)J recombination and CSR of IgG and IgE, but not IgA, and that IgG CSR is dependent on the canonical c-NHEJ pathway, whereas IgA CSR is more dependent on the alternative A-EJ pathway.

    • Conglei Li
    • , Thergiory Irrazabal
    •  & Alberto Martin

  • Article
    | Open Access

    Marginal zone B cells differentiate into plasma cells rapidly in response to T-cell-independent antigens, but how they do so is not clear. Here the authors show TACI cooperates with TLR signalling to drive mTOR activity and subsequent class switching and plasmablast differentiation.

    • Jordi Sintes
    • , Maurizio Gentile
    •  & Andrea Cerutti

  • Article
    | Open Access

    T cells help B cells to differentiate into antibody-producing plasma cells. Here the authors show that T cells produce interleukin-2 to activate ERK/ELK1 and suppress BACH2 expression by modulating the BACH2 super-enhancer, thereby altering BACH2 downstream transcription programs for plasma cell differentiation.

    • Nicolas Hipp
    • , Hannah Symington
    •  & Céline Delaloy

  • Article
    | Open Access

    CRISPR-Cas9 has been used to generate a range of genetic modifications including gene knock-outs and chromosomal rearrangements. Here the authors target the immunogloblin genes and demonstrate the induction of class switch recombination, opening up possibilities for research and antibody production.

    • Taek-Chin Cheong
    • , Mara Compagno
    •  & Roberto Chiarle

  • Article
    | Open Access

    Cell fate choices are often based on amplification of noise. Here the authors show that small initial differences in mitochondrial reactive oxygen species lead to bigger changes in mitochondrial mass and membrane potential, which then determine plasma cell fate choice of activated B cells.

    • Kyoung-Jin Jang
    • , Hiroto Mano
    •  & Manabu Sugai

  • Article
    | Open Access

    Class switch recombination diversifies antibody effector functions and requires expression of activation-induced cytidine deaminase (AID). In this study, ligation of the B-cell receptor and Toll-like receptors synergize to induce non-canonical NF-κB activation, AID expression and class switching recombination.

    • Egest J. Pone
    • , Jinsong Zhang
    •  & Paolo Casali

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