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.

The Year 2022 in biomaterials research: A perspective from the editors of six leading journals

“…We strive to provide a platform for biomaterials researchers to publish their best work in the journal and look forward to exciting breakthroughs in the coming year. Biomaterials are continually modified to control their mechanical properties for use in tissue engineering, 65 utilized for local release of bioactive moieties, 66 employed as model systems to study the immune system, 67 or designed to impede colonization by dangerous bacteria. 68 Over the last year, advances in biomaterials have been widespread with significant progress in innovative methods to deliver bioactive moieties and regulate how biomaterials interact with the immune system.…”

Advances in biomimetic hydrogels for organoid culture

“…3 illustrates the relationship between the biomimetic hydrogels and organoids. Meanwhile, some studies on biomimetic hydrogels have made some progress in the vascularisation of organoids, 64,69 the definition of a realistic microenvironment, 3,4 and the functionalisation of organoids. 38 These biomimetic hydrogels offer a good alternative to Matrigel and are expected to yield materials superior to animal-derived scaffolds.…”

“…Singh and co-workers developed a PEG-4MAL-based hydrogel 3D culture system to create immune organoids that exhibit an early memory B-cell-like phenotype. 4 They utilised a combination of hydrogels and cytokines to mimic the extracellular matrix and create a microenvironment that supports the growth and differentiation of the B cells. The operation of organoid passaging for long-term culture requires certain technology and may cause damage to the organoids.…”

“…[1][2][3] By providing a more realistic microenvironment for cells to grow and interact, organoids can better mimic the complex tissue architecture, cell-cell interactions, and physiological gradients found in vivo. 4,5 These enable researchers to study organ-specific processes such as morphogenesis, differentiation, and signalling, and to identify novel targets for therapeutic intervention. They can also be used as models for regenerative medicine, tissue engineering, and transplantation.…”

“…In recent years, most of the techniques widely used in organoid culture today come from modifications and optimisations based on some of these 3D culture methods. 4,7 There has been much research on 3D cell culture technology to explore how the extracellular matrix (ECM) could influence organoid formation and function in cell culture. 8 Clevers and co-workers first described the establishment of long-term culture conditions in Matrigel about six cycling Lgr5(+) single crypt stem cells initiating multiple crypt fission organoids.…”