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Circulating IgG3 increases in chronic HIV infection. Moir and colleagues describe a negative regulatory role of secreted IgG3 in response to chronic HIV infection through its action on nonconventional CD27– memory B cells.
Nemazee and colleagues show that PLD3 and PLD4 are endolysosomal exonucleases that digest ingested nucleic acids and thereby prevent activation of endosomal TLRs. Mice that lack PLD3 and PLD4 develop autoinflammatory disease.
Human follicular lymphomas arise from germinal center B cells. Milpied and colleagues use single-cell transcriptomic analysis to show that follicular lymphoma cells lose synchronized gene-expression patterns that characterize normal germinal center B cells.
Natural killer (NK) cells can acquire ‘memory’ signatures. Sun and colleagues examine the dynamic ATAC-seq and functional RNA-seq changes observed upon generation of NK cell memory and show distinct roles for transcription factors STAT1 and STAT4.
Signaling via the cytokine IL-9 receptor regulates humoral recall responses. Kitamura and colleagues report that IL-9 triggers memory B cells to proliferate and terminally differentiate into antibody-secreting cells rather than re-entering germinal centers.
Evidence of protective and homeostatic roles for IgE is relatively limited. Strid and colleagues demonstrate that γδ T cells induce switching to IgE that provides protection against experimentally induced epithelial cancer.
Soumelis and colleagues use RNA-based sequencing to define the transcriptional signatures of DC subsets and monocytes-macrophages in human primary breast cancer.
TCRs are often thought to be pre-clustered before T cell activation. Rossboth et al. use super-resolution microscopy and statistical image analysis to demonstrate that TCRs are in fact randomly distributed on resting T cells.
Lymphocytes interpret antigenic signals into a functional response. Richard et al. demonstrate that the overall qualitative response by CTLs is independent of TCR ligand strength; instead, ligands determine the rate and uniformity at which CTLs respond.
Foxo proteins are required for maintaining T cell quiescence. Turka and colleagues use a constitutively active Foxo1 in Treg cells to show that its downregulation is essential for maintaining their fitness in a competitive environment.
B cells need at least two signals to terminally differentiate into antibody-secreting cells. Pierce and colleagues show that persistent exposure to antigen in the absence of T cell help or ‘pathogen pattern motifs’ leads to B cell death via a calcium-dependent ‘metabolic timer’.
Regulatory factor X (RFX) is a transcription factor family comprising seven known members, yet the functional roles of RFX7 remain unknown. Guarda and colleagues show that RFX7 regulates natural killer (NK) cell survival and activity by limiting their cellular metabolism.
Tussiwand and colleagues show that pDCs develop predominantly from IL-7R+ lymphoid progenitor cells and that mature pDCs are transcriptionally and functionally heterogenous, on the basis of their lymphoid or myeloid lineage.
Typhoidal Salmonella is a major pathogen, but there is still a lack of knowledge about suitable vaccine antigens. Cerundolo and colleagues deep-phenotype bacteria-specific CD4+ T cells of Salmonella-infected volunteers to define cross-reactive and serovar-specific responses.
Liu and colleagues show that the ubiquitin E3 ligases Itch and WWP2 act together in regulating the strength of the TCR signal and differentiation toward the TH2 lineage.
The cytokines IL-17A and IL-17F bind via same receptor. Iwakura and colleagues demonstrate different functions for IL-17A and IL-17F in the gut, with the latter altering the production of antimicrobial peptides with consequent effects on the microbiota, the induction of Treg cells and immune-system homeostasis.
TIGIT is a co-inhibitory receptor associated with T cell exhaustion. Tian and colleagues demonstrate that TIGIT is the predominant inhibitory receptor on NK cells in both humans and mice and that its blockade enhances NK cell–dependent rejection of tumors in experimental models.
TCR signaling initiates a signaling cascade involving the kinases Lck and Zap70 and the adaptor LAT. Weiss and colleagues discover a proline-rich motif in LAT, which facilitates interactions among Lck, LAT and Zap70 for efficient TCR signaling.
The immune response to pathogens varies substantially among humans. Netea and colleagues show that integration of multi-omics data and deep phenotyping enables prediction of cytokine production in responses to pathogens.