title: Low-affinity B cells transport viral particles from the lung to the spleen to initiate antibody responses.
abstract: The lung is an important entry site for pathogens; its exposure to antigens results in systemic as well as local IgA and IgG antibodies. Here we show that intranasal administration of virus-like particles (VLPs) results in splenic B-cell responses with strong local germinal-center formation. Surprisingly, VLPs were not transported from the lung to the spleen in a free form but by B cells. The interaction between VLPs and B cells was initiated in the lung and occurred independently of complement receptor 2 and Fcγ receptors, but was dependent upon B-cell receptors. Thus, B cells passing through the lungs bind VLPs via their B-cell receptors and deliver them to local B cells within the splenic B-cell follicle. This process is fundamentally different from delivery of blood or lymph borne particulate antigens, which are transported into B cell follicles by binding to complement receptors on B cells.
authors.affiliation: Research Department, Cytos Biotechnology, CH-8952 Zurich-Schlieren,  Switzerland.
authors.forename: Juliana
authors.initials: J
authors.lastname: Bessa
authors.forename: Franziska
authors.initials: F
authors.lastname: Zabel
authors.forename: Alexander
authors.initials: A
authors.lastname: Link
authors.forename: Andrea
authors.initials: A
authors.lastname: Jegerlehner
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Hinton
authors.forename: Nicole
authors.initials: N
authors.lastname: Schmitz
authors.forename: Monika
authors.initials: M
authors.lastname: Bauer
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Kündig
authors.forename: Philippe
authors.initials: P
authors.lastname: Saudan
authors.forename: Martin F
authors.initials: MF
authors.lastname: Bachmann
mesh_terms: D000281:Administration, Intranasal; D019264:Adoptive Transfer; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000956:Antigens, Viral / Q000008:administration & dosage / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology*; D002465:Cell Movement / Q000276:immunology; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis; D008168:Lung / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D017464:Receptors, Complement 3d / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000821:virology; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000097:blood / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; C499172:Fcgr2b protein, mouse; D007074:Immunoglobulin G; D011947:Receptors, Antigen, B-Cell; D017464:Receptors, Complement 3d; D017452:Receptors, IgG; D058425:Vaccines, Virus-Like Particle