Cutting edge: innate immunity conferred by B cells is regulated by caspase-8.
Caspase-8 is an essential component of death receptor-mediated apoptosis. Along with Fas-associated death domain protein, it is also essential for T cell proliferation in response to antigenic or mitogenic stimuli. To determine whether caspase-8 is also required for B cell proliferation, we generated mice with a B cell-specific Casp8 deficiency. Unlike T cells, caspase-8 was not required for Ag receptor-driven proliferation or Ab formation. Rather, Casp8-deficient B cells failed to proliferate in response to dsRNA and LPS, ligands for TLR3 and TLR4, respectively, but responded normally to the TLR9 agonist CpG DNA. Similarly, Ab production to trinitrophenol-LPS was selectively reduced in B cell-specific Casp8-deficient mice. The activation of NF-kappaB or IFN regulatory factor 3 was found to be unaffected by the loss of caspase-8, implicating it in a novel pathway important for some forms of innate immunity mediated by B cells.
Beisner
Daniel R
DR
Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Ch'en
Irene L
IL
Kolla
Ravi V
RV
Hoffmann
Alexander
A
Hedrick
Stephen M
SM
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D053181:Caspase 8; D020169:Caspases / Q000172:deficiency / Q000276:immunology* / Q000502:physiology; D049109:Cell Proliferation; D007113:Immunity, Innate; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000276:immunology
C493487:Tlr4 protein, mouse; C495370:Tlr9 protein, mouse; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; C505526:Casp8 protein, mouse; D053181:Caspase 8; D020169:Caspases