Deciphering the Human Germinal Center: A Review of Models to Study T–B Cell Interactions

Interactions between T- and B cells in the germinal center reaction are instrumental for the initiation, maintenance, and downregulation of the human adaptive immune response, leading to the production of antigen-specific antibodies and long-lasting immunological memory. Replicating the human immune system remains challenging, with an over-reliance on animal models with limited translational accuracy. There is an increasing need for new tools that accurately model human immune function. This review evaluates existing 2D and 3D in vitro and ex vivo human models for their ability to reproduce the germinal center reaction, with a particular focus on T- and B-cell interaction. We conclude that although current models are able to replicate certain features of the germinal center reaction, no current model is able to completely replicate the complex human GC process. We outline the challenges in recreating a fully functional germinal center and suggest future directions of research to improve existing models, ultimately bringing us closer to completely reproducing the human lymph node.