title: Scarcity of autoreactive human blood IgA+memory B cells.
abstract: Class-switched memory B cells are key components of the "reactive" humoral immunity, which ensures a fast and massive secretion of high-affinity antigen-specific antibodies upon antigenic challenge. In humans, IgA class-switched (IgA+) memory B cells and IgA antibodies are abundant in the blood. Although circulating IgA+memory B cells and their corresponding secreted immunoglobulins likely possess major protective and/or regulatory immune roles, little is known about their specificity and function. Here, we show that IgA+and IgG+memory B-cell antibodies cloned from the same healthy humans share common immunoglobulin gene features. IgA and IgG memory antibodies have comparable lack of reactivity to vaccines, common mucosa-tropic viruses and commensal bacteria. However, the IgA+memory B-cell compartment contains fewer polyreactive clones and importantly, only rare self-reactive clones compared to IgG+memory B cells. Self-reactivity of IgAs is acquired following B-cell affinity maturation but not antibody class switching. Together, our data suggest the existence of different regulatory mechanisms for removing autoreactive clones from the IgG+and IgA+memory B-cell repertoires, and/or different maturation pathways potentially reflecting the distinct nature and localization of the cognate antigens recognized by individual B-cell populations.
authors.affiliation: Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris, France.|CNRS-URA 1961, Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Prigent
authors.affiliation: Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris, France.|CNRS-URA 1961, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Lorin
authors.affiliation: Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris, France.|CNRS-URA 1961, Paris, France.
authors.forename: Ayrin
authors.initials: A
authors.lastname: Kök
authors.affiliation: Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris, France.|CNRS-URA 1961, Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Hieu
authors.affiliation: Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris, France.|CNRS-URA 1961, Paris, France.
authors.forename: Salomé
authors.initials: S
authors.lastname: Bourgeau
authors.affiliation: Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris, France. hugo.mouquet@pasteur.fr.|CNRS-URA 1961, Paris, France. hugo.mouquet@pasteur.fr.
authors.forename: Hugo
authors.initials: H
authors.lastname: Mouquet
mesh_terms: D000915:Antibody Affinity; D000916:Antibody Diversity; D000917:Antibody Formation; D001323:Autoantibodies / Q000378:metabolism*; D001324:Autoantigens / Q000378:metabolism; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000502:physiology*; D060966:Clonal Selection, Antigen-Mediated; D002999:Clone Cells; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000378:metabolism; D007156:Immunologic Memory; D059010:Single-Cell Analysis
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G
keywords: Autoreactivity; IgA Antibodies; Immunoglobulin genes; Memory B cells; Polyreactivity