ABS 077: Engineering Biomaterial-Based Immune Organoids to Model Germinal Center Dynamics and B Cell Maturation

Zhe “Monica” Zhong ¹ ² ³ , Manuel Quiñones-Pérez ¹ ² , Zhonghao Dai ¹ ² , Valeria M. Juarez ¹ ² , Eshant Bhatia ¹ ² , Sonika Tatipalli ¹ , and Ankur Singh ¹ ² ³

¹ Wallace H. Coulter Department of Biomedical Engineering
² Parker H Petit Institute for Bioengineering & Bioscience
³ George W. Woodruff School of Mechanical Engineering

Van Wickle (2025) Volume 1, ABS077

Introduction: The immune system plays a critical role in health and disease, and the ability to modulate immune responses has significant implications for treating infections, autoimmune disorders, and cancer. The germinal center (GC) reaction is a critical component of adaptive immunity, driving B cell maturation, antibody diversification, and long-term immune memory. However, studying GC dynamics in vivo presents challenges due to the complexity of the lymph node microenvironment. To address this limitation, this study explains the development of polyethylene glycol (PEG)-based immune organoids that recapitulate key aspects of GC biology ex vivo. These organoids allow us to investigate the effects of polymer end-point chemistry, integrin ligands, and antigen presentation on B cell phenotype. Within lymph nodes, GC formation enables B cells to undergo somatic hypermutation and affinity maturation, ultimately leading to the selection of high-affinity antibody-producing plasma cells or memory B cells. This study outlines the fabrication and characterization of these synthetic immune organoids, employing flow cytometry, cytokine detection assays, and RNA sequencing to assess B cell proliferation and maturation. Organoids from peripheral blood mononuclear cells have proven to give more sustained GC reactions than those from tonsil cells, allowing less invasive and longer-term studies. By providing a controllable and reproducible platform to study immune responses and GC dynamics, our work advances the understanding of adaptive immunity and offers insights for vaccine development, immunotherapy strategies, and personalized medicine.