title: Human isotype-dependent inhibitory antibody responses against Mycobacterium tuberculosis.
abstract: Accumulating evidence from experimental animal models suggests that antibodies play a protective role against tuberculosis (TB). However, little is known about the antibodies generated upon Mycobacterium tuberculosis (MTB) exposure in humans. Here, we performed a molecular and functional characterization of the human B-cell response to MTB by generating recombinant monoclonal antibodies from single isolated B cells of untreated adult patients with acute pulmonary TB and from MTB-exposed healthcare workers. The data suggest that the acute plasmablast response to MTB originates from reactivated memory B cells and indicates a mucosal origin. Through functional analyses, we identified MTB inhibitory antibodies against mycobacterial antigens including virulence factors that play important roles in host cell infection. The inhibitory activity of anti-MTB antibodies was directly linked to their isotype. Monoclonal as well as purified serum IgA antibodies showed MTB blocking activity independently of Fc alpha receptor expression, whereas IgG antibodies promoted the host cell infection. Together, the data provide molecular insights into the human antibody response to MTB and may thereby facilitate the design of protective vaccination strategies.
authors.affiliation: Research Group Molecular Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.|Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.|B Cell Immunology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Natalie
authors.initials: N
authors.lastname: Zimmermann
authors.affiliation: Research Group Molecular Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Thormann
authors.affiliation: Research Group Molecular Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Anne-Britta
authors.initials: AB
authors.lastname: Köhler
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Aki
authors.initials: A
authors.lastname: Imai-Matsushima
authors.affiliation: U1019 - UMR 8204 - CIIL - Centre for Infection and Immunity of Lille, University of Lille, Lille, France.|CNRS, UMR 8204, Lille, France.|Inserm, U1019, Lille, France.|CHU Lille, Lille, France.|Institut Pasteur de Lille, Lille, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Locht
authors.affiliation: Center for Microbial Interface Biology, Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA.
authors.forename: Eusondia
authors.initials: E
authors.lastname: Arnett
authors.affiliation: Center for Microbial Interface Biology, Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA.
authors.forename: Larry S
authors.initials: LS
authors.lastname: Schlesinger
authors.affiliation: Department of Infectious Diseases and Respiratory Medicine, Charité University Medical Center, Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Zoller
authors.affiliation: Department of Infectious Diseases and Respiratory Medicine, Charité University Medical Center, Berlin, Germany.
authors.forename: Mariana
authors.initials: M
authors.lastname: Schürmann
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Stefan He
authors.identifier: 0000-0001-9866-8268
authors.initials: SH
authors.lastname: Kaufmann
authors.affiliation: Research Group Molecular Immunology, Max Planck Institute for Infection Biology, Berlin, Germany h.wardemann@dkfz.de.|B Cell Immunology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Hedda
authors.initials: H
authors.lastname: Wardemann
mesh_terms: D000907:Antibodies, Bacterial / Q000276:immunology* / Q000302:isolation & purification; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D007132:Immunoglobulin Isotypes
keywords: 
  Mycobacterium tuberculosis
  ; B cells; antibodies; infection; isotype