Low-affinity B cells transport viral particles from the lung to the spleen to initiate antibody responses

Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20566-71. doi: 10.1073/pnas.1206970109. Epub 2012 Nov 20.

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.

MeSH terms

  • Administration, Intranasal
  • Adoptive Transfer
  • Animals
  • Antibodies, Viral / biosynthesis
  • Antigens, Viral / administration & dosage
  • Antigens, Viral / blood
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / virology*
  • Cell Movement / immunology
  • Female
  • Immunoglobulin G / biosynthesis
  • Lung / immunology
  • Lung / virology
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Antigen, B-Cell / immunology
  • Receptors, Complement 3d / immunology
  • Receptors, IgG / immunology
  • Spleen / immunology
  • Spleen / virology
  • Vaccines, Virus-Like Particle / administration & dosage
  • Vaccines, Virus-Like Particle / blood
  • Vaccines, Virus-Like Particle / immunology*

Substances

  • Antibodies, Viral
  • Antigens, Viral
  • Fcgr2b protein, mouse
  • Immunoglobulin G
  • Receptors, Antigen, B-Cell
  • Receptors, Complement 3d
  • Receptors, IgG
  • Vaccines, Virus-Like Particle