B lymphocytes and macrophages release cell membrane deposited C3-fragments on exosomes with T cell response-enhancing capacity.
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.
Papp
Krisztián
K
Immunology Research Group, Hungarian Academy of Sciences, Budapest, Hungary.
Végh
Péter
P
Prechl
József
J
Kerekes
Krisztina
K
Kovács
János
J
Csikós
György
G
Bajtay
Zsuzsa
Z
Erdei
Anna
A
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001665:Binding Sites; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology*; D003167:Complement Activation / Q000276:immunology; D003179:Complement C3b / Q000276:immunology*; D006801:Humans; D007700:Kinetics; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011485:Protein Binding; D011951:Receptors, Complement / Q000276:immunology; D017464:Receptors, Complement 3d / Q000276:immunology; D022142:Secretory Vesicles / Q000276:immunology* / Q000648:ultrastructure; D044967:Serum; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013997:Time Factors
D011951:Receptors, Complement; D017464:Receptors, Complement 3d; D003179:Complement C3b