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Impaired dendritic cell maturation and increased TH2 responses in PIR-B−/− mice

Abstract

Mice deficient for paired immunoglobulin (Ig)-like receptor B (PIR-B) show defective regulation of receptor-mediated activation in antigen-presenting cells. Older PIR-B−/− mice had an increased number of peritoneal B1 cells. Splenic PIR-B−/− B2 cells were constitutively activated and proliferated much more than those from wild-type mice upon B cell receptor ligation. T helper type 2 (TH2)-prone humoral responses were augmented in PIR-B−/− mice upon immunization with T-dependent antigens, including increased interleukin 4 and decreased interferon-γ responses, as well as enhanced IgG1 and IgE production. Impaired maturation of dendritic cells (DCs), possibly due to perturbed intracellular signaling, was responsible for the skewed responses. Thus, PIR-B is critical for B cell suppression, DC maturation and for balancing TH1 and TH2 immune responses.

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Figure 1: Disruption of mouse Pirb.
Figure 2: Flow cytometric analysis of B cell development in wild type and PIR-B−/− mice.
Figure 3: Hypersensitive PIR-B−/− B cells to BCR stimulation
Figure 4: Augmented tyrosine phosphorylation in PIR-B−/− B cells.
Figure 5: Enhanced TH2-type responses to TD antigen in PIR-B−/− mice.
Figure 6: DCs of PIR-B−/− mice show impaired maturation and reduced IL-12 production and induce a TH2-prone response in wild-type mice by adoptive transfer.
Figure 7: Perturbed signaling of PIR-B−/− DCs.

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Acknowledgements

We thank M. D. Cooper, H. Kubagawa, A. Kudo, H. Karasuyama, M. Ono and K. Takatsu for reagents and helpful advice and D. Snell for critical reading of the manuscript. Supported by the CREST Program of Japan Science and Technology Corporation (JST) and a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to T. T.).

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Correspondence to Toshiyuki Takai.

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Ujike, A., Takeda, K., Nakamura, A. et al. Impaired dendritic cell maturation and increased TH2 responses in PIR-B−/− mice. Nat Immunol 3, 542–548 (2002). https://doi.org/10.1038/ni801

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