title: Functional capacities of human IgM memory B cells in early inflammatory responses and secondary germinal center reactions.
abstract: The generation and functions of human peripheral blood (PB) IgM(+)IgD(+)CD27(+) B lymphocytes with somatically mutated IgV genes are controversially discussed. We determined their differential gene expression to naive B cells and to IgM-only and IgG(+) memory B cells. This analysis revealed a high similarity of IgM(+)(IgD(+))CD27(+) and IgG(+) memory B cells but also pointed at distinct functional capacities of both subsets. In vitro analyses revealed a tendency of activated IgM(+)IgD(+)CD27(+) B cells to migrate to B-cell follicles and undergo germinal center (GC) B-cell differentiation, whereas activated IgG(+) memory B cells preferentially showed a plasma cell (PC) fate. This observation was supported by reverse regulation of B-cell lymphoma 6 and PR domain containing 1 and differential BTB and CNC homology 1, basic leucine zipper transcription factor 2 expression. Moreover, IgM(+)IgD(+)CD27(+) B lymphocytes preferentially responded to neutrophil-derived cytokines. Costimulation with catecholamines, carcinoembryonic antigen cell adhesion molecule 8 (CEACAM8), and IFN-γ caused differentiation of IgM(+)IgD(+)CD27(+) B cells into PCs, induced class switching to IgG2, and was reproducible in cocultures with neutrophils. In conclusion, this study substantiates memory B-cell characteristics of human IgM(+)IgD(+)CD27(+) B cells in that they share typical memory B-cell transcription patterns with IgG(+) post-GC B cells and show a faster and more vigorous restimulation potential, a hallmark of immune memory. Moreover, this work reveals a functional plasticity of human IgM memory B cells by showing their propensity to undergo secondary GC reactions upon reactivation, but also by their special role in early inflammation via interaction with immunomodulatory neutrophils.
authors.affiliation: Institute of Cell Biology (Cancer Research).
authors.forename: Marc
authors.initials: M
authors.lastname: Seifert
authors.affiliation: Institute of Cell Biology (Cancer Research).
authors.forename: Martina
authors.initials: M
authors.lastname: Przekopowitz
authors.affiliation: Institute of Cell Biology (Cancer Research).
authors.forename: Sarah
authors.initials: S
authors.lastname: Taudien
authors.affiliation: Institute of Cell Biology (Cancer Research).
authors.forename: Anna
authors.initials: A
authors.lastname: Lollies
authors.affiliation: Institute of Cell Biology (Cancer Research).
authors.forename: Viola
authors.initials: V
authors.lastname: Ronge
authors.affiliation: Institute of Cell Biology (Cancer Research).
authors.forename: Britta
authors.initials: B
authors.lastname: Drees
authors.affiliation: Institute for Transfusion Medicine.
authors.forename: Monika
authors.initials: M
authors.lastname: Lindemann
authors.affiliation: Department of Dermatology.
authors.forename: Uwe
authors.initials: U
authors.lastname: Hillen
authors.affiliation: Institute of Medical Psychology and Behavioural Immunobiology, and.
authors.forename: Harald
authors.initials: H
authors.lastname: Engler
authors.affiliation: Institute of Anatomy, Medical Faculty, University of Duisburg-Essen, Essen 45122, Germany.
authors.forename: Bernhard B
authors.initials: BB
authors.lastname: Singer
authors.affiliation: Institute of Cell Biology (Cancer Research), ralf.kueppers@uk-essen.de.
authors.forename: Ralf
authors.initials: R
authors.lastname: Küppers
mesh_terms: D000704:Analysis of Variance; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D018858:Germinal Center / Q000276:immunology*; D006801:Humans; D007072:Immunoglobulin D / Q000378:metabolism; D007075:Immunoglobulin M / Q000276:immunology* / Q000378:metabolism; D007156:Immunologic Memory / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D008856:Microscopy, Fluorescence; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism
chemical_list: D007072:Immunoglobulin D; D007075:Immunoglobulin M; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
keywords: IgM memory B-cell functions; early inflammatory response; germinal center reentry