Engineering early memory B‐cell‐like phenotype in hydrogel‐based immune organoids

Memory B cells originate in response to antigenic stimulation in B-cell follicles of secondary lymphoid organs where naive B cells undergo maturation within a subanatomical microenvironment, the germinal centers. The understanding of memory B-cell immunology and its regulation is based primarily on sophisticated experiments that involve mouse models. To date, limited evidence exists on whether memory B cells can be successfully engineered ex vivo, specifically using biomaterials-based platforms that support the growth and differentiation of B cells. Here, we report the characterization of a recently reported maleimide-functionalized poly(ethylene glycol) (PEG) hydrogels as immune organoids towards the development of early memory B-cell phenotype and germinal center-like B cells. We demonstrate that the use of interleukin 9 (IL9), IL21, and bacterial antigen presentation as outer membrane-bound fragments drives the conversion of naive, primary murine B cells to early memory phenotype in ex vivo immune organoids. These findings describe the induction of early memory B-cell-like phenotype in immune organoids and highlight the potential of synthetic organoids as a platform for the future development of antigen-specific bona fide memory B cells for the study of the immune system and generation of therapeutic antibodies.