Protocol for generating human tonsil immune organoids with epithelial and germinal center layers using low-Matrigel

Dandan Meng1, Han Ding1, Qiyu Deng1

  • 1Institute of Biopharmaceutical and Health Engineering (iBHE), Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.

STAR Protocols
|February 21, 2026
PubMed

Tonsil immune organoids traditionally include either epithelial layers or immune compartments, failing to recapitulate the integrated physiological microenvironment of human tonsils. Here, we present a protocol to generate tonsil immune organoids that recapitulate both epithelial and germinal center-like structures using a low-concentration Matrigel transwell system. We describe organoid assembly, immune stimulation, and evaluation of epithelial architecture and germinal center formation. This platform provides a versatile tool for dissecting human immune responses, assessing vaccines, discovering antibodies, and exploring autoimmune mechanisms.

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