Roadmap to a plasma cell: Epigenetic and transcriptional cues that guide B cell differentiation

• Type of Material: Article
• Authors: Christopher Scharer, Emory University; Keenan J Wiggins, Emory University
• Language: English
• Date: 2020-12-05
• Publisher: WILEY
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
• Final Published Version (URL): http://dx.doi.org/10.1111/imr.12934
• Title of Journal or Parent Work: IMMUNOLOGICAL REVIEWS
• Volume: 300
• Issue: 1
• Start Page: 54
• End Page: 64
• Grant/Funding Information: Funding support was provided by the National Institutes of Health grants 1R01AI148471 and 5R01CA095318 to C.D.S.
• Keywords: cell division; PROLIFERATION; NF-KAPPA-B; B cell; II GENE-EXPRESSION; Life Sciences & Biomedicine; secreting cell; DIVISION; plasma cell; CHROMATIN; GERMINAL CENTER B; Science & Technology; antibody‐ Immunology; GENERATION; transcription factor; SECRETING CELLS; SUPER-ENHANCERS; epigenetic; EZH2

Abstract

Antibody-secreting cells (ASCs) or plasma cells secrete antibodies and form a cornerstone of humoral immunity. B cells that receive activation signals in the presence or absence of T cells initiate a differentiation program that requires epigenetic and transcriptional reprogramming in order to ultimately form ASC. Reprogramming is accomplished through the interplay of transcription factors that initiate gene expression programs and epigenetic mechanisms that maintain these programs and cell fates. An important consideration is that all of these factors are operating in the context of cell division. Recent technical advances now allow mechanistic studies to move beyond genetic studies to identify the promoters and enhancer repertoires that are regulated by epigenetic mechanisms and transcription factors in rare cell types and differentiation stages in vivo. This review will detail efforts to integrate transcriptional and epigenetic changes during B cell differentiation with cell division in vivo. What has emerged is a multiphased differentiation model that requires distinct transcription factors and epigenetic programs at each step. The identification of markers that define each phase will help facilitate the manipulation of B cell differentiation for vaccine development or to treat diseases where antibodies are a component.