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

Abstract 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.