Atypical B-cells (ABCs) are observed across infections, yet their ontogeny and differentiation remain unclear. Using high-dimensional flow cytometry, single-cell transcriptomics, V(D)J sequencing, and functional assays in samples from individuals with malaria and healthy donors, we identify markers of cellular origin while tracking ABC differentiation. Early ABCs express CD11c and arise predominantly from memory B-cells. Two intermediate states originate from germinal center-derived and marginal zone-like B-cells. Pseudotime and lineage analyses reveal trajectories marked by progressive loss of CD24 and CD27, which is recapitulated in vitro, defining bona fide differentiation programs. Differentiation culminates in late ABCs lacking CD24, CD27, and CD21, while expressing CD11c, T-bet, and NKG7 at high levels, exhibiting partial overlap with double-negative-2 B-cells. Early and intermediate stages show greater plasma-cell differentiation potential and cytokine production capacity, whereas later stages acquire transcriptomic signatures of antigen presentation and association with microbial particles, defining stage-dependent functions that reconcile conflicting ABC roles. Comparable ABC populations occur in healthy blood and tonsils, with tissue-associated class switching and CD86 expression consistent with recent T-cell interaction. This framework consolidates ABC definitions along a single differentiation axis and clarifies their cellular origins.

Simulated microgravity provides a controlled perturbation for testing how loss of mechanical load affects human tissues. After 24 hours in rotating-wall vessels, neural, cardiac and tonsil organoids developed tissue-specific transcriptional responses that overlapped published spaceflight datasets, accompanied by higher transcriptomic-age estimates in neural and cardiac models, altered cardiac-organoid contraction dynamics and modified tonsil-organoid antiviral gene-expression signatures. These findings establish a multi-organoid framework for studying acute responses to gravitational unloading.

T follicular helper (Tfh) cells provide help to B cells for antibody class switching and affinity maturation and are critical for germinal center (GC) formation. The frequency of Tfh cells has proven to be a valuable marker for predicting durable neutralizing antibody responses; conversely, the expansion of dysfunctional Tfh cells and increased T follicular regulatory (Tfr) cells are associated with suboptimal antibody responses. Given that the pig is becoming an appealing preclinical model for vaccine evaluation, a better understanding of porcine Tfh and Tfr cell populations is required. Novel reagents to detect CXCR5 and PD-1 were generated and deployed in a high-dimensional flow cytometry panel to identify putative Tfh and Tfr cells in porcine blood and lymphoid tissues. Higher frequencies of CXCR5+PD-1-BCL6-CD4+ and CXCR5hiPD-1+BCL6+CD4+ T cells, putative Tfh and GC Tfh cells, respectively, were detected in tonsils compared with other tissues, while higher frequencies of FoxP3+CXCR5+BCL6-CD4+ (putative Tfr) and FoxP3+CXCR5hiBCL6+CD4+ (putative GC Tfr) cells were present in the tracheobronchial lymph nodes. In an in vitro coculture model, both CXCR5hiPD-1+CD4+ and CXCR5+PD-1-CD4+ Tfh cells supported greater B cell proliferation, plasma cell formation, and antibody production than CXCR5-CD4+ T cells. A staining panel developed to profile cytokine and activation-induced marker expression revealed that following T cell receptor stimulation, CXCR5hiBCL6+CD4+ and CXCR5+BCL6-CD4+ cells expressed greater levels of CD40L, ICOS, and IL-4 than non-Tfh cells, resembling findings in human Tfh cells. These data lay the foundation for further studies on porcine Tfh and Tfr cells, and the exploration of strategies to harness these cells for improved vaccine-induced immunity.

Enzyme replacement therapy (ERT) with intravenous idursulfase is the standard of care for patients with mucopolysaccharidosis II (MPS II; Hunter syndrome). Data are limited for children aged ≤12 months. This retrospective study evaluated outcomes with early ERT.

This case presents a female in her 20s with biopsy-confirmed cutaneous leukocytoclastic vasculitis (LCV) and significant gastrointestinal (GI) symptoms, manifesting as recurrent rectal bleeding, abdominal pain and maculopapular rash. The patient's symptoms emerged shortly after treatment with phenoxymethylpenicillin for tonsillitis. Investigations revealed left-sided colitis with distinctive endoscopic findings. Skin biopsy confirmed cutaneous LCV; however, colonic biopsies demonstrated non-specific inflammation without histological evidence of vasculitis. Therefore, GI vasculitic involvement could not be confirmed. Negative autoimmune serology excluded primary autoimmune disorders. Following treatment with prednisolone and mesalazine, the patient's symptoms resolved and she showed sustained improvement. While clinical improvement occurred after corticosteroid therapy, this response is non-specific and does not confirm GI vasculitis. Given the absence of vasculitic features on GI histology, the relationship between cutaneous LCV and colitis in this case remains associative rather than proven. This case underscores the importance of diagnostic caution when extracutaneous manifestations are suspected in LCV.

Pancytopenia is a diagnostic challenge due to its broad differential diagnosis, including infections and hematological malignancies. Parvovirus B19 infection is a recognized but uncommon cause of transient pancytopenia. However, positive viral serology or viremia may lead to diagnostic anchoring and delay the identification of underlying malignant disorders. We report the case of a 17-year-old previously healthy female presenting with persistent fever and tonsillitis. Laboratory investigations revealed pancytopenia with agranulocytosis. Blood serology and polymerase chain reaction (PCR) were positive for Parvovirus B19. The peripheral blood smear was normal. An initial diagnosis of virus-related pancytopenia was established. Despite supportive treatment, including granulocyte colony-stimulating factor, transfusions, and intravenous immunoglobulins, pancytopenia persisted. Bone marrow aspiration and biopsy were performed. The bone marrow aspiration showed a hypercellular marrow without abnormal cells by flow cytometry within the conventional blast gate. Subsequent pathological examination of the biopsy revealed massive blast infiltration consistent with acute promyelocytic leukemia. The patient rapidly developed disseminated intravascular coagulation, and atypical promyelocytes later appeared in the peripheral blood smear. Targeted treatment with all-trans retinoic acid and arsenic trioxide was initiated, leading to remission. This case highlights the risk of delayed diagnosis when pancytopenia is attributed to viral infection. Persistent cytopenia, even in the presence of positive Parvovirus B19 testing and a normal blood smear, should prompt early bone marrow examination to exclude underlying hematological malignancy.

Classically, B and T cells are differentiated by their mutually exclusive expression of surface markers such as CD3 and CD20, but it is now established that a few percent of T cells in human blood display also CD20. We analyzed CD3[+]CD20[+] cells in detail by combining single-cell proteogenomics, FACS, and ImageStream. Thereby, we identified CD3[+] B cells and found that about 40% of plasmablasts displayed CD3 in both blood and tonsils. In tonsils, where T-B interactions occur, about 80% of follicular helper T (Tfh) cells displayed CD20. In vitro, coactivation of T and B cells induced marker exchange via trogocytosis. We refer to the resulting cells as "masquerading" lymphocytes and analyzed them in multiple sclerosis (MS). CD20[+] T cells were markedly enriched in cerebrospinal fluid, exhibited cytotoxic gene signatures, accumulated in perivascular inflammatory cuffs, and showed increased myelin antigen reactivity. Anti-CD20 therapy (ofatumumab) not only depleted masquerading lymphocytes but also prevented their reinduction. Together, we identify CD3[+] B cells as footprints of T-B interactions thereby shifting the paradigm of lymphocyte-specific surface markers and implicate masquerading lymphocytes as active contributors to MS immunopathology.

Objective: To investigate the associations between snoring phenotypes recorded during preoperative drug-induced sleep endoscopy (DISE) and polysomnographic (PSG) metrics in children with obstructive sleep apnea (OSA). Methods: We retrospectively enrolled 175 children who underwent structured preoperative DISE between November 1, 2024 and January 1, 2026 because of confirmed/suspected obstructive sleep apnea (OSA) or adenoid-related upper airway assessment before orthodontic treatment. Among them, 108 were boys and 67 were girls, with a mean age of (6.9±1.9) years and a median age of 7.0 years (interquartile range, 5.6-8.0 years). All 175 children were included in the DISE descriptive analysis set to summarize structured DISE findings, snoring intensity, and snoring-source plane distribution. Of these, 136 children with DISE-documented snoring were included in the snoring-source plane analysis set to evaluate snoring-source planes and their combinations. Children were grouped according to DISE-recorded snoring intensity grades 0, 1, and 2, the number of five key snoring-source planes, and the presence or absence of each key plane. The five key snoring-source planes included the adenoid, soft palate, tonsil/lateral pharyngeal wall, tongue, and epiglottis. Among the 175 children, 108 with complete PSG outcomes and covariates including age, sex, and body mass index (BMI) were included in group comparisons and multivariable regression analyses. The primary outcome was obstructive apnea-hypopnea index (OAHI), and the secondary outcome was minimum peripheral oxygen saturation (SpO2 nadir). Group comparisons were performed using the Kruskal-Wallis test or Mann-Whitney U test. Multivariable linear regression was used to analyze the association between DISE snoring phenotypes and PSG metrics. Results: Among 175 children, 108 were boys (61.7%), the mean age was (6.9±1.9) years, and DISE documented snoring in 136(77.7%). In the PSG subgroup, median OAHI [interquartile range] across snoring grades 0, 1, and 2 was 3.6(2.2, 6.4), 5.8(3.0, 10.5), and 19.1(9.4, 45.6) events/h, respectively (H=14.43, P<0.001); corresponding SpO2 nadirs were 91.5%(89.0%, 94.0%), 93.0%(89.0%, 94.5%), and 84.0%(80.0%, 92.0%) (H=9.90, P=0.007). After adjustment for age, sex, and body mass index (BMI), snoring intensity remained independently associated with OAHI (β=0.45, P=0.010); each one-grade increase corresponded to a 56.8% increase in (OAHI+1) (95%CI 11.3%-120.9%). Conclusions: Snoring intensity during preoperative DISE was independently associated with PSG-derived obstructive burden in children with OSA. Tonsillar/lateral pharyngeal wall involvement predominated, while epiglottic and tongue-related planes were also common.