Type I Interferon Impairs Specific Antibody Responses Early during Establishment of LCMV Infection

• Published in: Frontiers in immunology Vol. 7; p. 564
• Main Authors: Daugan, Matthieu, Murira, Armstrong, Mindt, Barbara C, Germain, Amélie, Tarrab, Esther, Lapierre, Pascal, Fritz, Jörg H, Lamarre, Alain
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers 05.12.2016; Frontiers Media S.A
• Subjects: Antibody Formation; Immunology; immunopathology; Interferon Type I; lcmv; Life Sciences; neutralizing antibodies; neutralizing antibodies; antibody formation; LCMV; immunopathology; interferon type I
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2016.00564

Elicitation of type I interferon (IFN-I) has been shown to both enhance and impair cell-mediated immune responses in acute and persistent viral infections, respectively. Here, we show that, in addition to its effect on T cells, IFN-I drives impairment of specific antibody responses through interaction with B cells in the acute phase of lymphocytic choriomeningitis virus (LCMV) infection. This impairment was limited to the T cell-dependent B cell response and was associated with disruption of B cell follicles, development of hypergammaglobulinemia (HGG), and expansion of the T follicular helper cell population. Antigen-specific antibody responses were restored by ablation of IFN-I signaling through antibody-mediated IFN-I receptor blockade and B cell-specific IFN-I receptor knockout. Importantly, IFN-I receptor deficiency in B cells also accelerated the development of LCMV neutralizing antibodies and alleviated HGG. These results provide a potential therapeutic target toward efficient treatment measures that limit immunopathology in persistent viral infections.