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

• Type of Material: Article
• Authors: Pamela L. Graney, Cornell University; Zhe Zhong, Emory University; Sarah Post, Cornell University; Ilana Brito, Cornell University; Ankur Singh, Cornell University
• Language: English
• Date: 2022-04-07
• Publisher: WILEY
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022 Wiley Periodicals LLC.
• Final Published Version (URL): http://dx.doi.org/10.1002/jbm.a.37388
• Title of Journal or Parent Work: JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
• Volume: 110
• Issue: 8
• Start Page: 1435
• End Page: 1447
• Grant/Funding Information: The authors acknowledge funding support from the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health (5R01AI132738-03 and 5R21AI160136-02 awarded to A.S.), the Wellcome Leap HOPE Program (awarded to A.S.), the National Cancer Institute of the US National Institutes of Health (5R01CA238745-02 awarded to A.S.), and the Defense Threat Reduction Agency (HDTRA1-20-10004 awarded to A.S). Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the funding agency.
• Keywords: Materials Science, Biomaterials; hydrogel; GERMINAL-CENTER; DIFFERENTIATION; CUTTING EDGE; B cell; Engineering; RESPONSES; DYNAMICS; Materials Science; SELECTION; Technology; EXPRESSION; memory B cell; germinal center; Engineering, Biomedical; REGULATOR; bacteria; IL-21; Science & Technology
• Research Categories: Engineering, Biomedical; Biology, Cell

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.