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PreprintCC BY-NC-NDbioRxiv

Single-Cell and Spatial Analysis Reveals Retention of FCRL4⁺ Memory B Cells in Pediatric Tonsillar Hypertrophy

  1. 1Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.

Abstract

Pediatric tonsillar hypertrophy is a leading cause of sleep disordered breathing in children, yet the immune mechanisms sustaining tonsillar enlargement remain unclear. Using integrated single cell and spatial profiling of pediatric tonsils in a discovery cohort (n = 45) and independent validation cohort (n = 32), we identify a selective expansion and follicular retention of FCRL4+ memory B cells within the mantle zone of hypertrophic tonsils. These cells exhibit a quiescent, tissue-adapted phenotype characterized by NFATC1 repression and reciprocal RUNX1/RUNX2 regulation. Their accumulation is orchestrated by follicular type 1 regulatory T (Tr1) cells, which engage CTLA-4/CD86 checkpoint interactions to suppress plasma cell differentiation and reinforce a local immune tolerance program. Together, these interactions establish a persistent follicular niche enriched in regulatory FCRL4+ memory B cells. Our findings delineate a mechanistic Tr1/FCRL4+ B cell axis underlying follicular hypertrophy and highlight potential immunomodulatory targets for nonsurgical management of pediatric sleep-disordered breathing.

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BibTeX
@misc{baik2026singlecell,
  title = {{Single-Cell and Spatial Analysis Reveals Retention of FCRL4⁺ Memory B Cells in Pediatric Tonsillar Hypertrophy}},
  author = {J. Y. Baik and G. W. Park and S. Jin and J. Koh and Y. Moon and H. Seo and H. Y. Shin and C. Kim and T. Gu and M. Kim and D. H. Han and H. J. Kim},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.18.751603},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.18.751603v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - Single-Cell and Spatial Analysis Reveals Retention of FCRL4⁺ Memory B Cells in Pediatric Tonsillar Hypertrophy
AU  - J. Y. Baik
AU  - G. W. Park
AU  - S. Jin
AU  - J. Koh
AU  - Y. Moon
AU  - H. Seo
AU  - H. Y. Shin
AU  - C. Kim
AU  - T. Gu
AU  - M. Kim
AU  - D. H. Han
AU  - H. J. Kim
PY  - 2026
DA  - 2026/09/18
PB  - bioRxiv
DO  - 10.64898/2026.09.18.751603
UR  - https://www.biorxiv.org/content/10.64898/2026.09.18.751603v1
AB  - Pediatric tonsillar hypertrophy is a leading cause of sleep disordered breathing in children, yet the immune mechanisms sustaining tonsillar enlargement remain unclear. Using integrated single cell and spatial profiling of pediatric tonsils in a discovery cohort (n = 45) and independent validation cohort (n = 32), we identify a selective expansion and follicular retention of FCRL4+ memory B cells within the mantle zone of hypertrophic tonsils. These cells exhibit a quiescent, tissue-adapted phenotype characterized by NFATC1 repression and reciprocal RUNX1/RUNX2 regulation. Their accumulation is orchestrated by follicular type 1 regulatory T (Tr1) cells, which engage CTLA-4/CD86 checkpoint interactions to suppress plasma cell differentiation and reinforce a local immune tolerance program. Together, these interactions establish a persistent follicular niche enriched in regulatory FCRL4+ memory B cells. Our findings delineate a mechanistic Tr1/FCRL4+ B cell axis underlying follicular hypertrophy and highlight potential immunomodulatory targets for nonsurgical management of pediatric sleep-disordered breathing.
ER  -