Human isotype-dependent inhibitory antibody resonses against Mycobacterium tuberculosis
Authors
Natalie Zimmermann, Verena Thormann, Bo Hu, Anne-Britta Köhle, Aki Imai-Matsushima, Camille Locht, Eusondia Arnett, Larry S Schlesinger, Thomas Zoller, Mariana Schürmann, Stefan HE Kaufmann & Hedda Wardemann
Institution
Research Group Molecular Immunology, Max Planck Institute for Infection Bioloby & B cell, German Cancer Research Center
Country
Germany
Year
2016
Journal
EMBO Molecular Medecine
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.