Long-lived plasma cells maintain antibody titers that sustain humoral immunity, yet the physiological cues regulating their persistence remain incompletely understood. In this issue of Immunity, Zhu et al. reveal that fasting-induced β-hydroxybutyrate …
Regulated cell death is critical for both homeostasis and the response to infection. In this perspective, Tait and Oberst discuss how sub-lethal activation of canonical cell death pathways has lasting impacts on cells and tissues. These near-death cell…
Designing a universal influenza vaccine must address not only viral antigenic drift but also genetic variability in human antibody responses. In this issue of Immunity, two studies from the Karlsson-Hedestam lab (Corcoran et al. and Fischer et al.) int…
The immune system is a key contributor to organismal aging. Here, Ping et al. leverage single-cell multi-omics to construct a human immune aging clock, which pinpoints T cells as an aging nexus. RUNX1 orchestrates a transcriptional network that restrai…
Inducing broadly neutralizing antibodies (bnAbs) remains a challenge in HIV vaccine development. Mishra et al. show that an engineered germline-targeting HIV trimer, Q23-APEX-GT2, primes rare V2-apex bnAb precursors in humanized mice and outbred macaqu…
The generation of immune memory is at the crux of vaccine efficacy. Here, Crotty reviews the layers of adaptive immunity—T cell, B cells, and antibodies—and their integration to generate a holistic view of vaccine response. Common misconceptions and qu…
Vendramin et al. identify nonsense-mediated mRNA decay (NMD) as a central constraint on tumor antigenicity. Inhibiting the NMD kinase SMG1 stabilizes aberrant NMD-targeted transcripts and reveals a previously inaccessible class of non-canonical, non-mu…
Regulatory T (Treg) cells are phenotypically stable in inflammatory settings. Maltez et al. report that αCD40 immunotherapy induced conversion of Treg cells into FoxP3−Tbet+IFN-γ+ “ExTreg” cells within the tumor microenvironment. ExTreg cells exhibited…
Different clinical courses of HCV infection shape CD4+ T cell immunity. Reinscheid et al. show that a stem-like subset of CD4+ T cells arising during chronic infection is maintained after successful antiviral therapy and establishes long-term memory th…
Antibody responses following primary SARS-CoV-2 infection or mRNA vaccination are well described, but B cell phenotypes, receptor genetics, and antigen factors that determine initial viral variant binding breadth are less established. Wirz et al. find …
