Issues

In this issue of JEM, Yada et al. demonstrate that effective antibody affinity selection in germinal centers relies on the store-operated calcium entry (SOCE) component of the B cell receptor (BCR) signaling network.

Ayala et al. reveal that commensal bacteria elicit tonic type I interferons to prime dendritic cells and induce regulatory T cells that maintain a tolerogenic intestinal milieu.

Étienne Caron and colleagues discuss how immunopeptidomics and other peptide sequencing technologies could revolutionize the research for vaccine development, cancer immunotherapy, and treatment of neurodegenerative diseases and aging.

This review highlights classic and recent findings detailing molecular mechanisms of organ-specific functions of blood and lymphatic intestinal vessels, including nutrient absorption, epithelial cell maintenance, and immune cell recruitment. It also proposes future research directions for the field.

Lymphoid organ fibroblasts, known as fibroblastic reticular cells (FRCs), generate specialized niches in the tissue and coordinate immune cell interactions. De Martin and colleagues discuss basic concepts of FRC biology and how FRCs determine activation or attenuation of immune responses.

STIM-dependent calcium signaling after antigen recognition promotes GC B cell survival, leading to the maintenance and selection of high-affinity B cells during the GC reaction.

Commensal bacteria, such as Bacteroides fragilis, triggers type I IFN and IL-27 in DCs to influence Tregs through IL27RA signaling. The IFN gene signature in Tregs during inflammation highlights the role of the microbiota in maintaining tonic IFN to promote immune tolerance.

Segmented filamentous bacteria (SFB) induce the conversion of cognate CD4⁺ T cells to cytotoxic intraepithelial lymphocytes. The SFB-specific cytotoxic lymphocytes’ accumulation in the intraepithelial space as well as the regulation of epithelial cells’ turnover by them is dependent on small intestinal epithelial MHCII expression.

Lui et al. describe a human LCK variant causing partial loss-of-function (LOF), including defective TCR signaling and T cell development. Using mouse models, they show that while complete LCK LOF results in SCID, partial LCK LOF causes CID with autoimmunity.

Through single-cell transcriptomic analysis, Feng et al. identified a novel T follicular helper cell subset with stem cell–like transcriptional features and long-term survival ability, which gave rise to effector Tfh cells in recall immune responses.

Fu et al. demonstrate interchangeability between effector and tissue-resident memory (TRM) function for individual T cell clones with known (allo)recognition in a human non-lymphoid tissue during intestinal graft quiescence and rejection, providing novel insight into human TRM biology.

We show in polyclonal settings that GC B cell differentiation into plasma cells is affinity dependent, resulting in the generation of high-affinity serum responses. We profile GC cells poised for PC differentiation compared with GC B cells selected for further affinity maturation.

We established an Arl6ip1^−/− mouse model mimicking HSP with severe spastic paralysis and gait abnormalities. Neuroinflammation was identified as a key pathophysiological change. AAV9-ARL6IP1 delivery reduced limb paraplegia and gait abnormality, making ARL6IP1 a potential target for HSP gene therapy.

Solomon et al. establish that the Flt3⁺ multipotent progenitor (MPP4) compartment contains a quiescent/slow-cycling cell subpopulation, which has a prolonged in vivo hematopoietic potential and which constitutes a key transitional cell population between the hematopoietic stem cell and the lineage-biased MPP compartments.

The work demonstrates that a primary oncogene of B-ALL (i.e., PAX5-ELN) confers stem cell–like features to a subset of committed B cell progenitors, converting them to quiescent/resistant pre-LSCs. Moreover, EGR1 represents a strong candidate to control the quiescence/resistance of murine pre-LSCs and of blasts from patients.