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  • The G protein Gα13 is frequently lost in germinal center (GC) B cell-derived lymphomas. Mice that lack Gα13 exhibit increased proliferation of GC B cells in gut-draining lymph nodes where they go on to develop lymphomas. Dietary glutamine drives the proliferation of mucosal GC B cells that lack Gα13, potentially explaining the gut tropism of these lymphomas.

    Research Briefing
  • Immunological imprinting early in life has been proposed to influence the risk of infection by influenza viruses later on — but hard evidence for this has been lacking. A new study now shows how this can occur for influenza B viruses.

    • Isaac C. L. Chow
    • Sook-San Wong
    News & Views
  • We constructed a humanized (THX) mouse by grafting non-γ-irradiated, genetically myeloablated immunodeficient mouse neonates with human cord blood CD34+ cells, followed by 17β-estradiol hormonal conditioning. THX mice develop a human lymphoid and myeloid immune system, mount mature antibacterial and antiviral neutralizing antibody responses, and are amenable to develop lupus autoimmunity.

    Research Briefing
  • Muppidi and colleagues show that loss of Gα13 drives B cell lymphomas preferentially in the mesenteric lymph nodes. They find that Gα13 is required to counteract mTORC1 and Myc signaling that is driven by the availability of dietary glutamine.

    • Hang T. Nguyen
    • Moyi Li
    • Jagan R. Muppidi
    ArticleOpen Access
  • We performed transcriptional and chromatin accessibility profiling of TH17 cells to distinguish the pathways that regulate pathogenic versus non-pathogenic TH17 cell subsets. We show that TH17 cell functional heterogeneity is linked to distinct regulatory programs that are shared between TH17 cells and other CD4+ T cell states. BACH2 was identified as a key regulator of TH17 cell-mediated autoimmunity.

    Research Briefing
  • In this study, Uldrich and colleagues describe the crystal structure of the Vγ9Vδ2 T cell antigen receptor (TCR) interacting with BTN2A1 and demonstrate the existence of a second ligand that co-binds to a distinct epitope on Vγ9Vδ2 TCR. Using these data, the authors suggest a model of Vγ9Vδ2 TCR activation in which BTN2A1 and BTN3A1 are tethered to each other at the steady state, and must disengage to allow TCR binding.

    • Thomas S. Fulford
    • Caroline Soliman
    • Adam P. Uldrich
    Article
  • The EMBO workshop ‘Pathogen Immunity and Signaling’, held in San Servolo, Italy, from 8 to 12 April 2024, aimed to discuss cutting-edge advances in the understanding of antimicrobial defense mechanisms.

    • Mads Gyrd-Hansen
    • Anna Kajaste-Rudnitski
    • Matteo Iannacone
    Meeting Report
  • The thymus harbors a complex constitutively active inflammatory network with innate-like T cells representing one of its central nodes. Here, the authors show that these cells can induce tolerance to inflammation-associated self-antigens, a class of molecules that otherwise largely mirrors the spatial and temporal distribution of pathogen-derived antigens.

    • Yuanyuan You
    • Josefine Dunst
    • Taras Kreslavsky
    ArticleOpen Access
  • Our study shows that each stimulation experienced by memory B cells is epigenetically recorded in an IRF4-dependent manner, which determines the relative levels of BLIMP1 and BACH2 in B cells, and in turn dictates the likelihood that a memory B cell enters a germinal center or becomes a plasma cell after re-stimulation.

    Research Briefing
  • Extrafollicular and germinal center reactions are considered to represent sequential phases of a primary B cell response. A study now demonstrates the ability of autocrine IL-12 to promote extrafollicular differentiation into plasmablasts, while inhibiting germinal center responses.

    • Iñaki Sanz
    News & Views
  • Innate lymphoid cells (ILCs) exhibit remarkable plasticity, which makes using definitive markers to distinguish non-cytotoxic ILC1s and NK cells across different tissues difficult. New research now shows how the tissue microenvironments imprint diverse phenotypes that result in ILC1s and NK cells imitating each other.

    • M. Zeeshan Chaudhry
    • Gabrielle T. Belz
    News & Views
  • Qi and colleagues generate reporter mice that can track the stimulation history of individual B cells, a record epigenetically stored as progressive chromatin changes. This recording system revealed that the balance of B lymphocyte-induced maturation protein 1 (BLIMP1) to BTB domain and CNC homolog 2 (BACH2) predicts the fate of memory B cells upon recall challenge.

    • Wen Shao
    • Yifeng Wang
    • Hai Qi
    Article
  • Single-cell technologies have unveiled a complex understanding of NK cells that has led to variations in nomenclature and inconsistencies across the scientific literature. Here, Vivier and colleagues used these technologies to dissect the heterogeneity of NK cells, revealing three prominent NK cell subsets in healthy human blood.

    • Lucas Rebuffet
    • Janine E. Melsen
    • Eric Vivier
    ResourceOpen Access