Conserved Epigenetic Programming and Enhanced Heme Metabolism Drive Memory B Cell Reactivation

• Authors: Madeline J Price, Emory University; Christopher Scharer, Emory University; Anna K Kania, Emory University; Troy D Randall, University of Alabama Birmingham; Jeremy Boss, Emory University
• Journal Title: JOURNAL OF IMMUNOLOGY
• Volume: Volume 206, Number 7
• Publisher: AMER ASSOC IMMUNOLOGISTS | 2021-04-01, Pages 1493-1504
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.4049/jimmunol.2000551
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; TRANSCRIPTION FACTOR BACH2; REGULATORY ELEMENTS; GENE-EXPRESSION; T-BET; DIFFERENTIATION; RESPONSES; CHROMATIN; DURATION

Abstract

Memory B cells (MBCs) have enhanced capabilities to differentiate to plasma cells and generate a rapid burst of Abs upon secondary stimulation. To determine if MBCs harbor an epigenetic landscape that contributes to increased differentiation potential, we derived the chromatin accessibility and transcriptomes of influenza-specific IgM and IgG MBCs compared with naive cells. MBCs possessed an accessible chromatin architecture surrounding plasma cell-specific genes, as well as altered expression of transcription factors and genes encoding cell cycle, chemotaxis, and signal transduction processes. Intriguingly, this MBC signature was conserved between humans and mice. MBCs of both species possessed a heightened heme signature compared with naive cells. Differentiation in the presence of hemin enhanced oxidative phosphorylation metabolism and MBC differentiation into Absecreting plasma cells. Thus, these data define conserved MBC transcriptional and epigenetic signatures that include a central role for heme and multiple other pathways in augmenting MBC reactivation potential.