title: Nucleoprotein-specific nonneutralizing antibodies speed up LCMV elimination independently of complement and FcγR.
abstract: CD8(+) T cells have an essential role in controlling lymphocytic choriomeningitis virus (LCMV) infection in mice. Here, we examined the contribution of humoral immunity, including nonneutralizing antibodies (Abs), in this infection induced by low virus inoculation doses. Mice with impaired humoral immunity readily terminated infection with the slowly replicating LCMV strain Armstrong but showed delayed virus elimination after inoculation with the faster replicating LCMV strain WE and failed to clear the rapidly replicating LCMV strain Docile, which is in contrast to the results obtained with wild-type mice. Thus, the requirement for adaptive humoral immunity to control the infection was dependent on the replication speed of the LCMV strains used. Ab transfers further showed that LCMV-specific IgG Abs isolated from LCMV immune serum accelerated virus elimination. These Abs were mainly directed against the viral nucleoprotein (NP) and completely lacked virus neutralizing activity. Moreover, mAbs specific for the LCMV NP were also able to decrease viral titers after transfer into infected hosts. Intriguingly, neither C3 nor Fcγ receptors were required for the antiviral activity of the transferred Abs. In conclusion, our study suggests that rapidly generated nonneutralizing Abs specific for the viral NP speed up virus elimination and thereby may counteract T-cell exhaustion.
authors.affiliation: Department of Immunology, Institute of Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Straub
authors.forename: Oliver
authors.initials: O
authors.lastname: Schweier
authors.forename: Michael
authors.initials: M
authors.lastname: Bruns
authors.forename: Falk
authors.initials: F
authors.lastname: Nimmerjahn
authors.forename: Ari
authors.initials: A
authors.lastname: Waisman
authors.forename: Hanspeter
authors.initials: H
authors.lastname: Pircher
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D003165:Complement System Proteins / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009698:Nucleoproteins / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology; D019562:Viral Load / Q000276:immunology
chemical_list: D000974:Antibodies, Antinuclear; D000914:Antibodies, Viral; D009698:Nucleoproteins; D017452:Receptors, IgG; D003165:Complement System Proteins
keywords: CD8+ T cells; Fc gamma receptors; Humoral immunity; LCMV-binding antibodies