B lymphocytes undergo apoptosis because of FcgammaRIIb stress response to infection: a novel mechanism of cell death in sepsis.
Sepsis is predominantly characterized by proinflammatory signs in its initial phase, but can be also associated with immune suppression that can be a consequence of apoptotic cell death. The role of Fc receptors (FcRs) is poorly understood in this disease, and it was recently shown that, in addition to the promotion of opposite inflammatory responses, they are implicated in apoptosis. Using a model of peritonitis in mice that do not express activating FcRs, we tested the hypothesis that FcgammaRIIb, the only known immunoglobulin G receptor capable of inducing apoptosis, would participate in the induction of this kind of cell death during serious infection. The blocking of this receptor by a monoclonal antibody significantly decreased the number of apoptotic splenic B cells, demonstrating its involvement in apoptosis. FcgammaRIIb-mediated apoptosis was neither the result of increased TNFalpha levels nor was it associated with IL-10 production. Finally, the decreased apoptosis after mice treatment with FcgammaRIIb-blocking antibody was not sufficient to increase its survival. Thus, we conclude that although apoptosis is a multifactorial phenomenon in sepsis, one of these factors is the inhibitory immunoglobulin G receptor FcgammaRIIb. FcgammaRIIb stress response to infection is a novel mechanism that contributes to the comprehension of apoptosis in sepsis.
Pinheiro-da-Silva
Fabiano
F
Bichat Medical School, INSERM U699, 75870 Paris, France.
Chiamolera
Murilo
M
Charles
Nicolas
N
Kanamaru
Yutaka
Y
Velasco
Irineu Tadeu
IT
Benhamou
Marc
M
Monteiro
Renato C
RC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D010538:Peritonitis / Q000235:genetics / Q000276:immunology; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*; D018805:Sepsis / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000911:Antibodies, Monoclonal; C499172:Fcgr2b protein, mouse; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10