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      The Maintenance of Memory Plasma Cells

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          Abstract

          It is now well accepted that plasma cells can become long-lived (memory) plasma cells and secrete antibodies for months, years or a lifetime. However, the mechanisms involved in this process of humoral memory, which is crucial for both protective immunity and autoimmunity, still are not fully understood. This article will address a number of open questions. For example: Is longevity of plasma cells due to their intrinsic competence, extrinsic factors, or a combination of both? Which internal signals are involved in this process? What factors provide external support? What survival factors play a part in inflammation and autoreactive disease? Internal and external factors that contribute to the maintenance of memory long-lived plasma cells will be discussed. The aim is to provide useful additional information about the maintenance of protective and autoreactive memory plasma cells that will help researchers design effective vaccines for the induction of life-long protection against infectious diseases and to efficiently target pathogenic memory plasma cells.

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          Most cited references177

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          Origins and Mechanisms of miRNAs and siRNAs.

          Over the last decade, approximately 20-30 nucleotide RNA molecules have emerged as critical regulators in the expression and function of eukaryotic genomes. Two primary categories of these small RNAs--short interfering RNAs (siRNAs) and microRNAs (miRNAs)--act in both somatic and germline lineages in a broad range of eukaryotic species to regulate endogenous genes and to defend the genome from invasive nucleic acids. Recent advances have revealed unexpected diversity in their biogenesis pathways and the regulatory mechanisms that they access. Our understanding of siRNA- and miRNA-based regulation has direct implications for fundamental biology as well as disease etiology and treatment.
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            CD44: from adhesion molecules to signalling regulators.

            Cell-adhesion molecules, once believed to function primarily in tethering cells to extracellular ligands, are now recognized as having broader functions in cellular signalling cascades. The CD44 transmembrane glycoprotein family adds new aspects to these roles by participating in signal-transduction processes--not only by establishing specific transmembrane complexes, but also by organizing signalling cascades through association with the actin cytoskeleton. CD44 and its associated partner proteins monitor changes in the extracellular matrix that influence cell growth, survival and differentiation.
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              Plasma cell differentiation requires the transcription factor XBP-1.

              Considerable progress has been made in identifying the transcription factors involved in the early specification of the B-lymphocyte lineage. However, little is known about factors that control the transition of mature activated B cells to antibody-secreting plasma cells. Here we report that the transcription factor XBP-1 is required for the generation of plasma cells. XBP-1 transcripts were rapidly upregulated in vitro by stimuli that induce plasma-cell differentiation, and were found at high levels in plasma cells from rheumatoid synovium. When introduced into B-lineage cells, XBP-1 initiated plasma-cell differentiation. Mouse lymphoid chimaeras deficient in XBP-1 possessed normal numbers of activated B lymphocytes that proliferated, secreted cytokines and formed normal germinal centres. However, they secreted very little immunoglobulin of any isotype and failed to control infection with the B-cell-dependent polyoma virus, because plasma cells were markedly absent. XBP-1 is the only transcription factor known to be selectively and specifically required for the terminal differentiation of B lymphocytes to plasma cells.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                05 April 2019
                2019
                : 10
                : 721
                Affiliations
                [1] 1Deutsches Rheuma-Forschungszentrum Berlin—A Leibniz Institute , Berlin, Germany
                [2] 2Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Charité Mitte, Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie , Berlin, Germany
                Author notes

                Edited by: Simone Cenci, San Raffaele Hospital (IRCCS), Italy

                Reviewed by: Paolo Casali, University of Texas Health Science Center San Antonio, United States; Lee Ann Garrett-Sinha, University at Buffalo, United States

                *Correspondence: Falk Hiepe falk.hiepe@ 123456charite.de

                This article was submitted to B Cell Biology, a section of the journal Frontiers in Immunology

                †These authors have contributed equally to this work

                Article
                10.3389/fimmu.2019.00721
                6464033
                31024553
                0d39e8d1-b4a2-4884-b6e6-c6b2de18b7d2
                Copyright © 2019 Khodadadi, Cheng, Radbruch and Hiepe.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 10 December 2018
                : 18 March 2019
                Page count
                Figures: 1, Tables: 2, Equations: 0, References: 217, Pages: 17, Words: 15827
                Categories
                Immunology
                Review

                Immunology
                plasma cells,memory plasma cells,long-lived plasma cells,maintenance,survival,bone marrow,inflammation,autoreactivity

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