B Lymphocytes and Macrophages Release Cell Membrane Deposited C3-fragments on Exosomes With T Cell Response-Enhancing Capacity

Mol Immunol. 2008 Apr;45(8):2343-51. doi: 10.1016/j.molimm.2007.11.021. Epub 2008 Jan 14.

Abstract

Recently exosomes have been shown to play important roles in several immune phenomena. These small vesicles contain MHC proteins along with co-stimulatory and adhesion molecules, and mediate antigen presentation to T cells. In the present study we show that upon incubation with autologous serum, murine macrophages and B cells--but not T lymphocytes--fix C3-fragments covalently to the cell membrane and release them on exosomes in a time dependent fashion. While in the case of human B lymphocytes CR2 has been shown to serve as the main C3b-acceptor site, here we clearly demonstrate that cells derived from CR1/2 KO animals also have the capacity to fix C3b covalently. This finding points to a major difference between human and murine systems, and suggests the existence of additional acceptor sites on the cell membrane. Here we show that C3-fragment containing exosomes derived from OVA loaded antigen presenting cells induce a significantly elevated T cell response in the presence of suboptimal antigen stimulus. These data reveal a novel function of cell surface-deposited C3-fragments and provide further evidence for the role of exosomes secreted by antigen presenting cells. Since fixation of C3b to plasma membranes can be substantial in the presence of pathogens; moreover tumor cells are also known to activate the complement system resulting in complement-deposition, C3-carrying exosomes released by these cells may play an important immunomodulatory role in vivo, as well.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • Binding Sites
  • Cell Line
  • Cell Membrane / immunology*
  • Complement Activation / immunology
  • Complement C3b / immunology*
  • Humans
  • Kinetics
  • Macrophages / cytology
  • Macrophages / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Protein Binding
  • Receptors, Complement / immunology
  • Receptors, Complement 3d / immunology
  • Secretory Vesicles / immunology*
  • Secretory Vesicles / ultrastructure
  • Serum
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Time Factors

Substances

  • Receptors, Complement
  • Receptors, Complement 3d
  • Complement C3b