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

B lymphocytes and macrophages release cell membrane deposited C3-fragments on exosomes with T cell response-enhancing capacity.

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Immunology Research Group, Hungarian Academy of Sciences, Budapest, Hungary.


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.

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