Germinal centers (GCs) play a central role in generating an effective immune response against infectious pathogens, and failures in their regulating mechanisms can lead to the development of autoimmune diseases and cancer. Although previous works study experimental systems of the immune response with mouse models that are immunized with specific antigens, our study focused on a real-life situation, with an ongoing GC response in a human lymph node (LN) involving multiple asynchronized GCs reacting simultaneously to unknown antigens. We combined laser capture microdissection of individual GCs from human LN with next-generation repertoire sequencing to characterize individual GCs as distinct evolutionary spaces. In line with well-characterized GC responses in mice, elicited by immunization with model antigens, we observe a heterogeneous clonal diversity across individual GCs from the same human LN. Still, we identify shared clones in several individual GCs, and phylogenetic tree analysis combined with paratope modeling suggest the re-engagement and rediversification of B-cell clones across GCs and expanded clones exhibiting shared antigen responses across distinct GCs, indicating convergent evolution of the GCs.

Intraoperative resection level in patients with Hirschsprung disease (HD) is determined by contrast enema, surgeon's intraoperative judgement and full thickness biopsy (FTB) identifying ganglia. This study aims to evaluate diagnostic accuracy of contrast enema and FTB in determination of resection level and whether this can be improved by measuring submucosal nerve fiber diameter. We retrospectively analyzed contrast enema and intraoperative FTBs obtained in our center, determining diagnostic accuracy for level of resection. Gold standard was pathological examination of resection specimen. Secondly, we matched transition zone pull-through (TZPT) patients with non-TZPT patients, based on age and length of resected bowel, to blindly compare nerve fibers diameters between two groups using group comparison. From 2000-2021, 209 patients underwent HD surgery of whom 180 patients (138 males; median age at surgery: 13 weeks) with 18 TZPTs (10%) were included. Positive predictive value of contrast enema was 65.1%. No caliber change was found in patients with total colon aganglionosis (TCA). Negative predictive value of surgeon's intraoperative judgement and FTB in determining resection level was 79.0% and 90.0% (91.2% single-stage, 84.4% two-stage surgery) respectively. Mean nerve fiber diameter in TZPT was 25.01 µm (SD= 5.63) and in non-TZPT 24.35 µm (SD= 6.75) (p = 0.813). Determination of resection level with combination of contrast enema, surgeon's intraoperative judgement and FTB results in sufficient diagnostic accuracy in patients with HD. If no caliber change is seen with contrast enema, TCA should be considered. Resection level or transition zone cannot be determined by assessment of submucosal nerve fiber diameter in FTB. clinical research paper.

Chronic B-cell receptor signals incited by cognate antigens are believed to play a crucial role in the pathogenesis of mucosa-associated lymphoid tissue lymphomas. We have explored the immunoglobulin variable regions (IGHV) expressed by 124 ocular adnexal MALT lymphomas (OAML) and tested the in vitro reactivity of recombinant IgM derived from 23 OAMLs. Six of 124 OAMLs (5%) were found to express a high-affinity stereotyped rheumatoid factor. OAMLs have a biased IGHV4-34 usage, which confers intrinsic super auto-antigen reactivity with poly-N-acetyllactosamine (NAL) epitopes, present on cell surface glycoproteins of erythrocytes and B cells. Twenty-one OAMLs (17%) expressed IGHV4-34-encoded B-cell receptors. Five of the 23 recombinant OAML IgMs expressed IGHV4-34, four of which bound to the linear NAL i epitope expressed on B cells but not to the branched NAL I epitope on erythrocytes. One non-IGHV4-34-encoded OAML IgM was also reactive with B cells. Interestingly, three of the 23 OAML IgMs (13%) specifically reacted with proteins of U1-/U-snRNP complexes, which have been implicated as cognate-antigens in various autoimmune diseases such as systemic lupus erythematosus and mixed connective tissue disease. The findings indicate that local autoimmune reactions are instrumental in the pathogenesis of a substantial fraction of OAMLs.

Background: Low-grade fibromyxoid sarcoma (LGFMS) is a rare malignant fibroblastic tumor that often appears deceptively benign. Accurate diagnosis is challenging due to its variable morphology and low mitotic activity. This systematic review provides a comprehensive overview of LGFMS and its subtypes. Methods: A systematic search of PubMed and Embase up to September 2025 identified 273 studies, complemented by four institutional cases from Amsterdam UMC. Individual patient data were pooled to analyze clinical presentation, diagnostic approaches, treatment modalities, and outcomes. Results: In total, 773 patients were included, with a median age of 35 years and equal gender distribution. Tumors were predominantly deep-seated (80%), most commonly located in the thigh or pelvis. MUC4 positivity (96%) and FUS-CREB3L2 fusion (47%) were the most consistent diagnostic markers. Surgery was the mainstay of treatment (98%), with R0 resection achieved in 36% of cases and R1 in 15%. Adjuvant therapies, including chemotherapy and radiotherapy, were rarely used and showed limited efficacy. After a median follow-up of 3.0 years, 19% developed local recurrence and 21% developed metastases. R0 resections were associated with significantly better recurrence-free survival than R1 resection (p < 0.05). Conclusions: LGFMS exhibits indolent histology but potential for late recurrence and metastasis, warranting prolonged radiological follow-up and multicenter studies to evaluate adjuvant strategies.