Epigenetic gene regulation in plasma cells

• Authors: Dillion G Patterson, Emory University; Anna K Kania, Emory University; Zhihong Zuo, Emory University; Christopher Scharer, Emory University; Jeremy Boss, Emory University
• Journal Title: IMMUNOLOGICAL REVIEWS
• Volume: Volume 303, Number 1
• Publisher: WILEY | 2021-05-19, Pages 8-22
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1111/imr.12975
• Subjects: Health Sciences, Immunology; Biology, Microbiology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; B cell differentiation; cell division; epigenetics; heme; plasma cells; transcriptomics; UNFOLDED PROTEIN RESPONSE; GERMINAL CENTER B; IMMUNOGLOBULIN-SECRETING CELLS; TRANSCRIPTION FACTOR BLIMP-1; BONE-MARROW; ANTIBODY-RESPONSES; ER STRESS; METHYLTRANSFERASE ACTIVITY; TERMINAL DIFFERENTIATION; CHROMATIN ARCHITECTURE

Abstract

Humoral immunity provides protection from pathogenic infection and is mediated by antibodies following the differentiation of naive B cells (nBs) to antibody-secreting cells (ASCs). This process requires substantial epigenetic and transcriptional rewiring to ultimately repress the nB program and replace it with one conducive to ASC physiology and function. Notably, these reprogramming events occur within the framework of cell division. Efforts to understand the relationship of cell division with reprogramming and ASC differentiation in vivo have uncovered the timing and scope of reprogramming, as well as key factors that influence these events. Herein, we discuss the unique physiology of ASC and how nBs undergo epigenetic and genome architectural reorganization to acquire the necessary functions to support antibody production. We also discuss the stage-wise manner in which reprogramming occurs across cell divisions and how key molecular determinants can influence B cell fate outcomes.