B-Cell Signalling
Innate immunity conferred by B cells is regulated by caspase-8. Beisner, D. R. et al. J. Immunol. 175, 3469–3473 (2005)
In addition to its role in death-receptor-mediated apoptosis, caspase-8 is essential for antigen-induced T-cell proliferation. To investigate the role of caspase-8 in B-cell activation, Beisner et al. generated mice in which only B cells were deficient in caspase-8. Caspase-8-deficient B cells showed no defect in proliferation after B-cell-receptor stimulation. By contrast, caspase-8 was required for B-cell survival and proliferation in response to stimulation through Toll-like receptor 3 (TLR3) or TLR4 (but not TLR9). Activation of both nuclear factor-κB and interferon-regulatory factor 3 occurred normally following stimulation of the caspase-8-deficient B cells through TLR3 or TLR4, leading the authors to suggest that caspase-8 is part of a novel signalling cascade in B cells that is downstream of specific innate immune receptors.
Natural Killer Cells
Recognition of peptide–MHC class I complexes by activating killer immunoglobulin-like receptors. Stewart, C. A. et al. Proc. Natl Acad. Sci. USA 102, 13224–13229 (2005)
Although activating killer-cell immunoglobulin-like receptors (KIR-Ss) are homologous to inhibitory KIRs (KIR-Ls), which bind certain HLA class I allotypes, activating KIR ligands are poorly defined. Stewart et al. used tetramers of the activating KIR KIR2DS1 to show that cells infected with Epstein–Barr virus express a KIR2DS1 ligand. Further analysis indicated that, similar to its inhibitory counterpart (KIR2DL1), KIR2DS1 bound HLA-C2 MHC class I molecules. Binding was dependent on transporter associated with antigen processing and required the same repertoire of MHC-class-I-bound peptides as did KIR2DL1 binding. But the affinity of KIR2DL1 for a given peptide–HLA-C2 complex was greater than that of KIR2DS1, and KIR2DS1–ligand interactions could not always trigger natural killer (NK)-cell cytotoxicity, indicating that these activating signals are part of a finely tuned network of signals that control NK-cell activation.
Autoimmunity
Nasal vaccination with a proteosome-based adjuvant and glatiramer acetate clears β-amyloid in a mouse model of Alzheimer disease. Frenkel, D. et al. J. Clin. Invest. 115, 2423–2433 (2005)
Previous attempts to produce a vaccine for Alzheimer's disease have failed, owing to unacceptable side-effects in patients. In this paper, the authors took advantage of compounds that have been approved for human use and designed a vaccine that reduces amyloid plaques in a mouse model of Alzheimer's disease. Mice were immunized intranasally with a proteosome-based adjuvant and glatiramer acetate, a synthetic co-polymer that is used to treat multiple sclerosis. The vaccine activated microglial cells, which then cleared amyloid in the brain without evidence of harmful side-effects. The therapeutic effect did not require the presence of antibody, because it was retained in B-cell-deficient mice. It is hoped that this vaccine will have more success in the clinic.
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In Brief. Nat Rev Immunol 5, 745 (2005). https://doi.org/10.1038/nri1723
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DOI: https://doi.org/10.1038/nri1723