Gene Symbol: Pirb
Description: paired Ig-like receptor B
Alias: Gp91, LIR-3, Lilrb3, PIR-B, leukocyte immunoglobulin-like receptor subfamily B member 3, cell-surface glycoprotein p91, leukocyte immunoglobulin-like receptor 3, leukocyte immunoglobulin-like receptor, subfamily B (with TM and ITIM domains), member 3, paired immunoglobulin-like receptor B
Species: mouse
Products:     Pirb

Top Publications

  1. Takai T. Paired immunoglobulin-like receptors and their MHC class I recognition. Immunology. 2005;115:433-40 pubmed
    ..Thus, PIR-A and PIR-B constitute a novel and physiologically important MHC class I recognition system. ..
  2. Syken J, GrandPre T, Kanold P, Shatz C. PirB restricts ocular-dominance plasticity in visual cortex. Science. 2006;313:1795-800 pubmed
    ..Here, we demonstrate that Paired-immunoglobulin-like receptor B (PirB), a major histocompatibility complex class I (MHCI) receptor, is expressed in subsets of neurons throughout the ..
  3. Yamashita Y, Fukuta D, Tsuji A, Nagabukuro A, Matsuda Y, Nishikawa Y, et al. Genomic structures and chromosomal location of p91, a novel murine regulatory receptor family. J Biochem. 1998;123:358-68 pubmed
    ..The gene was found to be located on human chromosome 19q13.3-13.4. These results establish the existence of a novel set of potent regulatory receptors in mouse and man, similar but different from the KIR family. ..
  4. Munitz A, Cole E, Beichler A, Groschwitz K, Ahrens R, Steinbrecher K, et al. Paired immunoglobulin-like receptor B (PIR-B) negatively regulates macrophage activation in experimental colitis. Gastroenterology. 2010;139:530-41 pubmed publisher
    ..We examined the susceptibility of Pirb-/- and wild-type (WT) mice to dextran sodium sulfate (DSS)-induced colitis...
  5. Ho L, Uehara T, Chen C, Kubagawa H, Cooper M. Constitutive tyrosine phosphorylation of the inhibitory paired Ig-like receptor PIR-B. Proc Natl Acad Sci U S A. 1999;96:15086-90 pubmed
    ..These findings suggest a physiological inhibitory role for PIR-B that is regulated by endogenous MHC class I-like ligands...
  6. Ujike A, Takeda K, Nakamura A, Ebihara S, Akiyama K, Takai T. Impaired dendritic cell maturation and increased T(H)2 responses in PIR-B(-/-) mice. Nat Immunol. 2002;3:542-8 pubmed
    ..Thus, PIR-B is critical for B cell suppression, DC maturation and for balancing T(H)1 and T(H)2 immune responses. ..
  7. Mori Y, Tsuji S, Inui M, Sakamoto Y, Endo S, Ito Y, et al. Inhibitory immunoglobulin-like receptors LILRB and PIR-B negatively regulate osteoclast development. J Immunol. 2008;181:4742-51 pubmed
    ..Modulation of these regulatory receptors may be a novel way to control various skeletal system disorders and inflammatory arthritis. ..
  8. Pereira S, Zhang H, Takai T, Lowell C. The inhibitory receptor PIR-B negatively regulates neutrophil and macrophage integrin signaling. J Immunol. 2004;173:5757-65 pubmed
    ..These observations point to a nonredundant role for PIR-B in the regulation of leukocyte integrin signaling. ..
  9. Endo S, Sakamoto Y, Kobayashi E, Nakamura A, Takai T. Regulation of cytotoxic T lymphocyte triggering by PIR-B on dendritic cells. Proc Natl Acad Sci U S A. 2008;105:14515-20 pubmed publisher
    ..On surface plasmon resonance analysis, PIR-B and CD8alpha alpha were revealed to compete in binding to MHC-I. Our results may provide a novel strategy for regulating CTL-mediated immunity and diseases in a sterical manner. ..

More Information


  1. Mitsuhashi Y, Nakamura A, Endo S, Takeda K, Yabe Wada T, Nukiwa T, et al. Regulation of plasmacytoid dendritic cell responses by PIR-B. Blood. 2012;120:3256-9 pubmed publisher
    ..These results demonstrate a novel regulatory role for PIR-B in PDCs. ..
  2. Ma G, Pan P, Eisenstein S, Divino C, Lowell C, Takai T, et al. Paired immunoglobin-like receptor-B regulates the suppressive function and fate of myeloid-derived suppressor cells. Immunity. 2011;34:385-95 pubmed publisher
    ..immunoglobulin-like receptor B (PIR-B), also known as leukocyte immunoglobulin-like receptor subfamily B member 3 (LILRB3) in MDSC differentiation, and its role in tumor-induced immunity...
  3. Hayami K, Fukuta D, Nishikawa Y, Yamashita Y, Inui M, Ohyama Y, et al. Molecular cloning of a novel murine cell-surface glycoprotein homologous to killer cell inhibitory receptors. J Biol Chem. 1997;272:7320-7 pubmed
    ..Surface biotinylation and immunoprecipitation analysis verified the surface expression of the translation products on COS-1 cells transfected with the p91 cDNA, but the cells failed to show any Fc binding activity. ..
  4. Kubagawa H, Burrows P, Cooper M. A novel pair of immunoglobulin-like receptors expressed by B cells and myeloid cells. Proc Natl Acad Sci U S A. 1997;94:5261-6 pubmed
    ..The characteristics of the highly-conserved PIR-A and PIR-B genes and their coordinate cellular expression suggest a potential regulatory role in humoral, inflammatory, and allergic responses. ..
  5. Takai T, Nakamura A, Endo S. Role of PIR-B in autoimmune glomerulonephritis. J Biomed Biotechnol. 2011;2011:275302 pubmed publisher
    ..Thus, PIR-B is an important regulator of innate immunity mediated by TLR9 in B-1 cells, which can otherwise provoke autoimmunity when overactivated. ..
  6. Kubo T, Uchida Y, Watanabe Y, Abe M, Nakamura A, Ono M, et al. Augmented TLR9-induced Btk activation in PIR-B-deficient B-1 cells provokes excessive autoantibody production and autoimmunity. J Exp Med. 2009;206:1971-82 pubmed publisher
    ..The autoantibody production in PIR-B-deficient (Pirb(-/-)) mice was further augmented in combination with the Fas(lpr) mutation, which might be linked to the ..
  7. Imada M, Masuda K, Satoh R, Ito Y, Goto Y, Matsuoka T, et al. Ectopically expressed PIR-B on T cells constitutively binds to MHC class I and attenuates T helper type 1 responses. Int Immunol. 2009;21:1151-61 pubmed publisher
    ..Our findings suggest that T cell expression of PIR-B with the cis-interacting MHC class I is strictly prohibited in periphery so as to secure prompt immune responses. ..
  8. Zhang H, Meng F, Chu C, Takai T, Lowell C. The Src family kinases Hck and Fgr negatively regulate neutrophil and dendritic cell chemokine signaling via PIR-B. Immunity. 2005;22:235-46 pubmed
    ..These data support a model in which the Src family kinases Hck and Fgr function as negative regulators of myeloid cell chemokine signaling by maintaining the tonic phosphorylation of PIR-B. ..
  9. Masuda A, Nakamura A, Maeda T, Sakamoto Y, Takai T. Cis binding between inhibitory receptors and MHC class I can regulate mast cell activation. J Exp Med. 2007;204:907-20 pubmed
    ..Thus, the constitutive cis binding between LILRB2 or PIR-B and MHC class I has an essential role in regulating allergic responses. ..
  10. Nakamura A, Kobayashi E, Takai T. Exacerbated graft-versus-host disease in Pirb-/- mice. Nat Immunol. 2004;5:623-9 pubmed
    ..Thus, PIR-A and PIR-B are counteracting receptors that are essential for successful tissue transplantation and may regulate irrelevant reaction to autologous tissues in a constitutive way in physiological conditions. ..
  11. Munitz A, McBride M, Bernstein J, Rothenberg M. A dual activation and inhibition role for the paired immunoglobulin-like receptor B in eosinophils. Blood. 2008;111:5694-703 pubmed publisher
    ..We now report that Pirb was up-regulated in an eosinophil-dependent manner in the lungs of allergen-challenged and interleukin (IL)-13-..
  12. Karo Atar D, Moshkovits I, Eickelberg O, Konigshoff M, Munitz A. Paired immunoglobulin-like receptor-B inhibits pulmonary fibrosis by suppressing profibrogenic properties of alveolar macrophages. Am J Respir Cell Mol Biol. 2013;48:456-64 pubmed publisher
    ..Finally, leukocyte immunoglobulin-like receptor subfamily B member 3 (LILRB3)/immunoglobulin-like transcript-5, the human PIR-B orthologue, was expressed and up-regulated in lung biopsies ..
  13. Atwal J, Pinkston Gosse J, Syken J, Stawicki S, Wu Y, Shatz C, et al. PirB is a functional receptor for myelin inhibitors of axonal regeneration. Science. 2008;322:967-70 pubmed publisher
    ..With the use of expression cloning, we have found that paired immunoglobulin-like receptor B (PirB), which has been implicated in nervous system plasticity, is a high-affinity receptor for Nogo, MAG, and OMgp...
  14. Matsushita H, Endo S, Kobayashi E, Sakamoto Y, Kobayashi K, Kitaguchi K, et al. Differential but competitive binding of Nogo protein and class i major histocompatibility complex (MHCI) to the PIR-B ectodomain provides an inhibition of cells. J Biol Chem. 2011;286:25739-47 pubmed publisher
    ..Thus, we propose a novel mechanism by which PIR-B-mediated regulation is achieved differentially but competitively via MHCI and Nogo in cells of the immune system. ..
  15. Fujita Y, Endo S, Takai T, Yamashita T. Myelin suppresses axon regeneration by PIR-B/SHP-mediated inhibition of Trk activity. EMBO J. 2011;30:1389-401 pubmed publisher
    ..Our results thus identify a new molecular target to enhance regeneration of the injured CNS. ..
  16. Zheng J, Umikawa M, Cui C, Li J, Chen X, Zhang C, et al. Inhibitory receptors bind ANGPTLs and support blood stem cells and leukaemia development. Nature. 2012;485:656-60 pubmed publisher
    ..leukocyte immunoglobulin-like receptor B2 (LILRB2) and its mouse orthologue paired immunoglobulin-like receptor (PIRB) are receptors for several ANGPTLs...
  17. Adelson J, Barreto G, Xu L, Kim T, Brott B, Ouyang Y, et al. Neuroprotection from stroke in the absence of MHCI or PirB. Neuron. 2012;73:1100-7 pubmed publisher
    ..Here we examine a role for MHC class I (MHCI) H2-Kb and H2-Db, as well as PirB receptor. These molecules restrict synaptic plasticity and motor learning in the healthy brain...
  18. Yugami M, Odagiri H, Endo M, Tsutsuki H, Fujii S, Kadomatsu T, et al. Mice Deficient in Angiopoietin-like Protein 2 (Angptl2) Gene Show Increased Susceptibility to Bacterial Infection Due to Attenuated Macrophage Activity. J Biol Chem. 2016;291:18843-52 pubmed publisher
    ..Collectively, our findings suggest that macrophage-derived ANGPTL2 promotes an innate immune response in those cells by enhancing proinflammatory activity and NO production required to fight infection. ..
  19. Gou X, Zhang Q, Xu N, Deng B, Wang H, Xu L, et al. Spatio-temporal expression of paired immunoglobulin-like receptor-B in the adult mouse brain after focal cerebral ischaemia. Brain Inj. 2013;27:1311-5 pubmed publisher
    Paired immunoglobulin-like receptor-B (PirB) is another receptor, except for the Nogo receptor, that is involved in inhibition of axons regeneration after central nervous system injury...
  20. Nakayama M, Underhill D, Petersen T, Li B, Kitamura T, Takai T, et al. Paired Ig-like receptors bind to bacteria and shape TLR-mediated cytokine production. J Immunol. 2007;178:4250-9 pubmed
    ..aureus and enhanced TLR-mediated inflammatory responses to the bacteria. These data suggest a novel mechanism for innate immune regulation by paired Ig-like receptor family members. ..
  21. Scroggins S, Olivier A, Meyerholz D, Schlueter A. Characterization of regulatory dendritic cells that mitigate acute graft-versus-host disease in older mice following allogeneic bone marrow transplantation. PLoS ONE. 2013;8:e75158 pubmed publisher
    ..DCreg identified in older DCreg-treated BMT mice at d +3 showed significantly lower expression of PD-L1 and PIR B compared to DCreg from young DCreg-treated BMT mice...
  22. Ben Baruch Morgenstern N, Shik D, Moshkovits I, Itan M, Karo Atar D, Bouffi C, et al. Paired immunoglobulin-like receptor A is an intrinsic, self-limiting suppressor of IL-5-induced eosinophil development. Nat Immunol. 2014;15:36-44 pubmed publisher
    ..Subsequently, Pirb(-/-) mice displayed impaired aeroallergen-induced lung eosinophilia and induction of lung TH2 cell responses...
  23. Chen C, Kong D, Cooper M, Kubagawa H. Mast cell regulation via paired immunoglobulin-like receptor PIR-B. Immunol Res. 2002;26:191-7 pubmed
    ..This analysis suggests that PIR-B may serve to control mast cell activity. ..
  24. Zhou D, Collins C, Wu P, Brown E. Protein tyrosine phosphatase SHP-1 positively regulates TLR-induced IL-12p40 production in macrophages through inhibition of phosphatidylinositol 3-kinase. J Leukoc Biol. 2010;87:845-55 pubmed publisher
  25. Wang J, Shiratori I, Satoh T, Lanier L, Arase H. An essential role of sialylated O-linked sugar chains in the recognition of mouse CD99 by paired Ig-like type 2 receptor (PILR). J Immunol. 2008;180:1686-93 pubmed
    ..These findings indicate that sialylated O-linked sugar structures on CD99 play an important role in the recognition of PILR. ..
  26. Kim T, Vidal G, Djurisic M, William C, Birnbaum M, Garcia K, et al. Human LilrB2 is a ?-amyloid receptor and its murine homolog PirB regulates synaptic plasticity in an Alzheimer's model. Science. 2013;341:1399-404 pubmed publisher
    ..We report that murine PirB (paired immunoglobulin-like receptor B) and its human ortholog LilrB2 (leukocyte immunoglobulin-like receptor B2), ..
  27. Vidal G, Djurisic M, Brown K, Sapp R, Shatz C. Cell-Autonomous Regulation of Dendritic Spine Density by PirB. Eneuro. 2016;3: pubmed
    ..At this time, mice lacking paired Ig-like receptor B (PirB) have excess numbers of dendritic spines on L5 neurons; these spines persist and are thought to underlie the ..
  28. Fujita Y, Takashima R, Endo S, Takai T, Yamashita T. The p75 receptor mediates axon growth inhibition through an association with PIR-B. Cell Death Dis. 2011;2:e198 pubmed publisher
    ..Mice carrying a mutation in the p75 gene showed promotion of axonal regeneration after optic nerve injury. Thus, our results indicate that p75 has a critical role in axon growth inhibition in specific neuronal tracts. ..
  29. Jenner F, IJpma A, Cleary M, Heijsman D, Narcisi R, van der Spek P, et al. Differential gene expression of the intermediate and outer interzone layers of developing articular cartilage in murine embryos. Stem Cells Dev. 2014;23:1883-98 pubmed publisher
    ..The high representation of genes relevant to chondrocyte hypertrophy and endochondral ossification in the outer interzone suggests that it undergoes endochondral ossification. ..
  30. Chen C, Hurez V, Brockenbrough J, Kubagawa H, Cooper M. Paternal monoallelic expression of the paired immunoglobulin-like receptors PIR-A and PIR-B. Proc Natl Acad Sci U S A. 1999;96:6868-72 pubmed
  31. Arita K, Endo S, Kaifu T, Kitaguchi K, Nakamura A, Ohmori H, et al. Transcriptional activation of the Pirb gene in B cells by PU.1 and Runx3. J Immunol. 2011;186:7050-9 pubmed publisher
    ..However, the mechanism underlying transcriptional control of the genes for PIR-B and PIR-A (Pirb and Pira, respectively) remains to be clarified...
  32. Nakayama M, Kurokawa K, Nakamura K, Lee B, Sekimizu K, Kubagawa H, et al. Inhibitory receptor paired Ig-like receptor B is exploited by Staphylococcus aureus for virulence. J Immunol. 2012;189:5903-11 pubmed publisher
    ..Consequently, Pirb(-/-) mice infected with S...
  33. Bochner D, Sapp R, Adelson J, Zhang S, Lee H, Djurisic M, et al. Blocking PirB up-regulates spines and functional synapses to unlock visual cortical plasticity and facilitate recovery from amblyopia. Sci Transl Med. 2014;6:258ra140 pubmed publisher
    ..By acutely disrupting paired immunoglobulin-like receptor B (PirB) function at specific ages, we show that PirB actively represses neural plasticity throughout life...
  34. Fan X, Shi P, Dai J, Lu Y, Chen X, Liu X, et al. Paired immunoglobulin-like receptor B regulates platelet activation. Blood. 2014;124:2421-30 pubmed publisher
    Murine paired immunoglobulin-like receptors B (PIRB), as the ortholog of human leukocyte immunoglobulin-like receptor B2 (LILRB2), is involved in a variety of biological functions...
  35. Kondo Y, Jadlowiec C, Muto A, Yi T, Protack C, Collins M, et al. The Nogo-B-PirB axis controls macrophage-mediated vascular remodeling. PLoS ONE. 2013;8:e81019 pubmed publisher
    Nogo-B mediates vascular protection and facilitates monocyte- and macrophage-dependent vascular remodeling. PirB is an alternate receptor for Nogo-B, but a role for the Nogo-PirB axis within the vascular system has not been previously ..
  36. Omoto S, Ueno M, Mochio S, Takai T, Yamashita T. Genetic deletion of paired immunoglobulin-like receptor B does not promote axonal plasticity or functional recovery after traumatic brain injury. J Neurosci. 2010;30:13045-52 pubmed publisher
    ..Each of Nogo, MAG, and OMgp interacts with both the Nogo receptor (NgR) and paired immunoglobulin-like receptor B (PirB)...
  37. Nakamura Y, Fujita Y, Ueno M, Takai T, Yamashita T. Paired immunoglobulin-like receptor B knockout does not enhance axonal regeneration or locomotor recovery after spinal cord injury. J Biol Chem. 2011;286:1876-83 pubmed publisher
    ..These results indicate that PIR-B knock-out is not sufficient to induce extensive axonal regeneration after spinal cord injury. ..
  38. Liang S, Baibakov B, Horuzsko A. HLA-G inhibits the functions of murine dendritic cells via the PIR-B immune inhibitory receptor. Eur J Immunol. 2002;32:2418-26 pubmed
    ..This demonstration forms the basis for exploring and exploiting HLA-G molecules and immune inhibitory receptors in the development of a new therapeutic strategy to improve allogeneic graft survival. ..
  39. Dennis G, Stephan R, Kubagawa H, Cooper M. Characterization of paired Ig-like receptors in rats. J Immunol. 1999;163:6371-7 pubmed
    ..Southern blot analysis predicts the presence of multiple Pira genes and a single Pirb gene in the rat genome...
  40. Berg K, Carlberg K, Rohrschneider L, Siminovitch K, Stanley E. The major SHP-1-binding, tyrosine-phosphorylated protein in macrophages is a member of the KIR/LIR family and an SHP-1 substrate. Oncogene. 1998;17:2535-41 pubmed
    ..These observations identify SHP-1 interactions with and regulation of p91/PIR-B as a potential mechanism for inhibiting the signaling cascades linking extracellular stimuli to macrophage activation and/or development. ..
  41. Alley T, Cooper M, Chen M, Kubagawa H. Genomic structure of PIR-B, the inhibitory member of the paired immunoglobulin-like receptor genes in mice. Tissue Antigens. 1998;51:224-31 pubmed
    ..A microsatellite composed of the trinucleotide repeat AAG in the intron between exons 9 and 10 provides a useful marker for studying population genetics. ..
  42. Cai X, Yuan R, Hu Z, Chen C, Yu J, Zheng Z, et al. Expression of PirB protein in intact and injured optic nerve and retina of mice. Neurochem Res. 2012;37:647-54 pubmed publisher
    The aim of this study was to investigate the expression of PirB protein in intact mice ON (optic nerve) and retina, and to evaluate its change after ON injury. The mouse ON crush model was established...
  43. Ramasamy S, Yu F, Hong Yu Y, Srivats H, Dawe G, Ahmed S. NogoR1 and PirB signaling stimulates neural stem cell survival and proliferation. Stem Cells. 2014;32:1636-48 pubmed publisher
    ..In this study, we show that NogoA receptors, NogoR1 and PirB, are expressed in the ventricular zone where NSCs reside between E10.5 and 14.5 but not at E15.5...
  44. Nelson M, Metz A, Li S, Lowell C, Steele C. The absence of Hck, Fgr, and Lyn tyrosine kinases augments lung innate immune responses to Pneumocystis murina. Infect Immun. 2009;77:1790-7 pubmed publisher
    ..murina. Our results suggest that SFKs regulate innate lung responses to P. murina in a PIR-B-independent manner. ..
  45. Torii I, Oka S, Hotomi M, Benjamin W, Takai T, Kearney J, et al. PIR-B-deficient mice are susceptible to Salmonella infection. J Immunol. 2008;181:4229-39 pubmed
    ..These findings suggest that the disruption of PIR-A and PIR-B balance affects their regulatory roles in host defense to bacterial infection. ..
  46. Zhao Z, Deng B, Xu H, Zhang J, Mi Y, Meng X, et al. PirB Overexpression Exacerbates Neuronal Apoptosis by Inhibiting TrkB and mTOR Phosphorylation After Oxygen and Glucose Deprivation Injury. Cell Mol Neurobiol. 2017;37:707-715 pubmed publisher
    Previous studies have proven that paired immunoglobulin-like receptor B (PirB) plays a crucial suppressant role in neurite outgrowth and neuronal plasticity after central nervous system injury...
  47. Ukai H, Kawahara A, Hirayama K, Case M, Aino S, Miyabe M, et al. PirB regulates asymmetries in hippocampal circuitry. PLoS ONE. 2017;12:e0179377 pubmed publisher
    ..analyses on the hippocampal circuitry of mice with a knockout of the paired immunoglobulin-like receptor B (PirB), an MHCI receptor...
  48. Rothe K, Raulien N, Kohler G, Pierer M, Quandt D, Wagner U. Autoimmune arthritis induces paired immunoglobulin-like receptor B expression on CD4+ T cells from SKG mice. Eur J Immunol. 2017;47:1457-1467 pubmed publisher
    ..More importantly, a major population of PIR-B+ T cells in SKG mice appears to play an inhibitory role by way of their IFN-? production, since high frequencies of those cells ameliorate the disease. ..
  49. Raiker S, Lee H, Baldwin K, Duan Y, Shrager P, Giger R. Oligodendrocyte-myelin glycoprotein and Nogo negatively regulate activity-dependent synaptic plasticity. J Neurosci. 2010;30:12432-45 pubmed publisher
    ..and OMgp complex with the neuronal cell surface receptors Nogo receptor-1 (NgR1) and paired Ig-like receptor-B (PirB) to regulate neuronal morphology...
  50. Djurisic M, Vidal G, Mann M, Aharon A, Kim T, Ferrao Santos A, et al. PirB regulates a structural substrate for cortical plasticity. Proc Natl Acad Sci U S A. 2013;110:20771-6 pubmed publisher
    ..Here we show that the paired immunoglobulin-like receptor B (PirB) negatively regulates spine density, as well as the threshold for adult OD plasticity...
  51. Ben Baruch Morgenstern N, Mingler M, Stucke E, Besse J, Wen T, Reichman H, et al. Paired Ig-like Receptor B Inhibits IL-13-Driven Eosinophil Accumulation and Activation in the Esophagus. J Immunol. 2016;197:707-14 pubmed publisher
    ..We report that Pirb is upregulated in the esophagus after inducible overexpression of IL-13 (CC10-Il13(Tg) mice) and is overexpressed ..