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Enhanced Human Antigen-Specific B Cell Responses Using In Vitro 3D Tonsil Cultures Containing Stromal Cells.

Maaike V J Braham1,2,3, Marlon de Gast2,4, Liubov Babii1,2

  • 1Sanquin, Amsterdam, The Netherlands.

Advanced Healthcare Materials
|April 16, 2026
PubMed
Summary
This summary is machine-generated.

Researchers developed a 3D human lymphoid culture system to mimic germinal centers (GCs). This advanced model improves B cell survival and antibody production, offering a better platform for studying immune responses and vaccine development.

Keywords:
3D culture systemantibody‐secreting cellsfibroblastic reticular cellsgerminal center responsehydrogelorganoidvaccine

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Area of Science:

  • Immunology
  • Cell Biology
  • Biotechnology

Background:

  • Germinal centers (GCs) are crucial for antibody production but are complex to model in vitro.
  • Conventional 2D cultures do not fully replicate the intricate microenvironment of human GCs.

Purpose of the Study:

  • To develop a 3D human lymphoid culture system that better mimics the in vivo GC environment.
  • To enhance the study of B cell maturation, antibody production, and immune responses.

Main Methods:

  • Developed a 3D hydrogel culture system using human tonsil cells and fibroblastic reticular cells (FRCs).
  • Compared 2D and 3D cultures with and without FRCs, stimulating with viral antigens or vaccines.
  • Analyzed B and T cell survival, antibody production, cell differentiation, and GC-like polarization markers.

Main Results:

  • FRC-supported 3D cultures significantly improved B and T cell survival and promoted follicle-like structure formation.
  • 3D FRC-supported co-cultures yielded higher antigen-specific antibody levels and increased frequencies of antigen-specific B cells.
  • GC-like polarization was observed, with reduced cell death and bystander activation, and specific chemokine receptor expression on B cells.

Conclusions:

  • The 3D human lymphoid culture system provides a more physiologically relevant model for studying GC responses.
  • This platform facilitates mechanistic research and screening of vaccine immunogens and adjuvants.
  • The model's scalability supports high-throughput applications in immunology and vaccinology.