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

Baik, J. Y.; Park, G. W.; Jin, S.; Koh, J.; Moon, Y.; Seo, H.; Shin, H. Y.; Kim, C.; Gu, T.; Kim, M.; Han, D. H.; Kim, H. J.

doi:10.64898/2026.09.18.751603

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bioRxiv · 10.64898/2026.09.18.751603

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

Baik, J. Y.·Park, G. W.·Jin, S.·Koh, J.·Moon, Y.·Seo, H.·Shin, H. Y.·Kim, C.·Gu, T.·Kim, M.·Han, D. H.·Kim, H. J.

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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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Baik, J. Y., Park, G. W., Jin, S., Koh, J., Moon, Y., Seo, H., Shin, H. Y., Kim, C., Gu, T., Kim, M., Han, D. H., Kim, H. J.. 2026-09-24. Single-Cell and Spatial Analysis Reveals Retention of FCRL4⁺ Memory B Cells in Pediatric Tonsillar Hypertrophy. https://doi.org/10.64898/2026.09.18.751603

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