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Gene Review

MICB  -  MHC class I polypeptide-related sequence B

Homo sapiens

Synonyms: MIC-B, PERB11.2
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Disease relevance of MICB


High impact information on MICB


Biological context of MICB


Anatomical context of MICB

  • In vitro, UL16 interacts with MICB and ULBPs that are ligands for the stimulatory receptor NKG2D, expressed on NK cells and CD8(+)T cells [13].
  • The purpose of this study was to investigate the genetic polymorphisms and haplotypes of microsatellite locus in exon 5 of the MICA gene and intron 1 of the MICB gene and human leukocyte antigen-B (HLA-B) gene based on 106 samples of the Guangzhou Han population through means of polymerase chain reaction and the fluorescent technique (6-FAM) [12].
  • To elucidate the extent of MICB allelic variations, we sequenced exons 2 (alpha 1), 3 (alpha 2), 4 (alpha 3), and 5 (transmembrane) as well as introns 2 and 4 of this gene in 46 HLA homozygous B-cell lines [14].
  • From pairwise associations in the random panel and results for the homozygous cell lines it was possible to deduce the MICA and MICB microsatellite alleles present in many of the well-known Caucasoid extended haplotypes [15].
  • MICB was detected exclusively in the cytosol of primary tumors and cell lines [16].

Associations of MICB with chemical compounds


Physical interactions of MICB


Regulatory relationships of MICB

  • Experiments designed to test the functional significance of these observations revealed that brief interactions between NK cells and MICB expressing target cells led to a reduction in NKG2D-dependent NK cytotoxicity [21].

Other interactions of MICB

  • UL16 expression has been shown to promote intracellular accumulation of MICB, ULBP1 and 2 and thus, interfere with the immune response to HCMV-infected cells [13].
  • A preliminary linkage analysis of the MICB alleles with those of the closely located MICA and HLA-B genes revealed no conspicuous linkage disequilibrium between them, implying the presence of a potential recombination hotspot between the MICB and MICA genes [14].
  • MICA and ULBP2 expression decrease with increasing WHO grade of malignancy, while MICB and ULBP1 are expressed independently of tumour grade [22].
  • The distribution of the five alleles of MICA and the 13 alleles of MICB microsatellites, located, respectively, in MICA transmembrane exon 5 and in MICB intron 1, was examined in 133 healthy Italian individuals previously typed for HLA class I, class II and complement loci and for the TNFa microsatellite [15].
  • There was no difference between the cancer patients and controls for the genotypes of the AluyMICB locus within intron 1 of the MICB gene and the other three POALINs (AluyHJ, AluyHG and AluyHF) that are located within the genomic region of the HLA-A, -G and -F gene cluster [23].

Analytical, diagnostic and therapeutic context of MICB

  • We also detected increased sMICB levels in patient sera using a newly established MICB-specific enzyme-linked immunosorbent assay [24].
  • Transplantation of the MICB alpha2 domain confers UL16 binding capacity to MICA, and thus, diversification of the MICA alpha2 domain may have been driven by the selective pressure exerted by UL16 [10].
  • In this study, we report the expression of MICA and MICB in renal and pancreatic allograft biopsies, which were obtained due to clinical signs of rejection [17].
  • CONCLUSIONS.: This is the first study demonstrating variable levels of MICB expression in kidneys before transplantation and induction of MICB expression following renal transplantation [25].
  • MICB was typed by PCR using sequence-specific primers [26].


  1. ULBPs, novel MHC class I-related molecules, bind to CMV glycoprotein UL16 and stimulate NK cytotoxicity through the NKG2D receptor. Cosman, D., Müllberg, J., Sutherland, C.L., Chin, W., Armitage, R., Fanslow, W., Kubin, M., Chalupny, N.J. Immunity (2001) [Pubmed]
  2. Expression and role of MICA and MICB in human hepatocellular carcinomas and their regulation by retinoic acid. Jinushi, M., Takehara, T., Tatsumi, T., Kanto, T., Groh, V., Spies, T., Kimura, R., Miyagi, T., Mochizuki, K., Sasaki, Y., Hayashi, N. Int. J. Cancer (2003) [Pubmed]
  3. Eight novel MICB alleles, including a null allele, identified in gastric MALT lymphoma patients. Schroeder, M., Elsner, H.A., Kim, T.D., Blasczyk, R. Tissue Antigens (2004) [Pubmed]
  4. MICA rather than MICB, TNFA, or HLA-DRB1 is associated with susceptibility to psoriatic arthritis. González, S., Martínez-Borra, J., López-Vázquez, A., García-Fernández, S., Torre-Alonso, J.C., López-Larrea, C. J. Rheumatol. (2002) [Pubmed]
  5. Primary sclerosing cholangitis is associated to an extended B8-DR3 haplotype including particular MICA and MICB alleles. Wiencke, K., Spurkland, A., Schrumpf, E., Boberg, K.M. Hepatology (2001) [Pubmed]
  6. Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. Groh, V., Wu, J., Yee, C., Spies, T. Nature (2002) [Pubmed]
  7. Recognition of stress-induced MHC molecules by intestinal epithelial gammadelta T cells. Groh, V., Steinle, A., Bauer, S., Spies, T. Science (1998) [Pubmed]
  8. Human cytomegalovirus glycoprotein UL16 causes intracellular sequestration of NKG2D ligands, protecting against natural killer cell cytotoxicity. Dunn, C., Chalupny, N.J., Sutherland, C.L., Dosch, S., Sivakumar, P.V., Johnson, D.C., Cosman, D. J. Exp. Med. (2003) [Pubmed]
  9. HLA class I, NKG2D, and natural cytotoxicity receptors regulate multiple myeloma cell recognition by natural killer cells. Carbone, E., Neri, P., Mesuraca, M., Fulciniti, M.T., Otsuki, T., Pende, D., Groh, V., Spies, T., Pollio, G., Cosman, D., Catalano, L., Tassone, P., Rotoli, B., Venuta, S. Blood (2005) [Pubmed]
  10. Human cytomegalovirus-encoded UL16 discriminates MIC molecules by their alpha2 domains. Spreu, J., Stehle, T., Steinle, A. J. Immunol. (2006) [Pubmed]
  11. Nucleotide sequencing analysis of the 146-kilobase segment around the IkBL and MICA genes at the centromeric end of the HLA class I region. Shiina, T., Tamiya, G., Oka, A., Yamagata, T., Yamagata, N., Kikkawa, E., Goto, K., Mizuki, N., Watanabe, K., Fukuzumi, Y., Taguchi, S., Sugawara, C., Ono, A., Chen, L., Yamazaki, M., Tashiro, H., Ando, A., Ikemura, T., Kimura, M., Inoko, H. Genomics (1998) [Pubmed]
  12. Study on the haplotypes of MICA and MICB microsatellite and HLA-B locus in the Guangzhou Han population. Feng, M.L., Guo, X.J., Zhang, J.Y., Xie, J.H., Chen, L., Lu, Q., Yang, J.H., Ji, Y., Qian, K.C. Tissue Antigens (2004) [Pubmed]
  13. The human cytomegalovirus glycoprotein UL16 traffics through the plasma membrane and the nuclear envelope. Valés-Gómez, M., Winterhalter, A., Roda-Navarro, P., Zimmermann, A., Boyle, L., Hengel, H., Brooks, A., Reyburn, H.T. Cell. Microbiol. (2006) [Pubmed]
  14. Allelic variants of the human MHC class I chain-related B gene (MICB). Ando, H., Mizuki, N., Ota, M., Yamazaki, M., Ohno, S., Goto, K., Miyata, Y., Wakisaka, K., Bahram, S., Inoko, H. Immunogenetics (1997) [Pubmed]
  15. MICA and MICB microsatellite alleles in HLA extended haplotypes. Bolognesi, E., Dalfonso, S., Rolando, V., Fasano, M.E., Praticò, L., Momigliano-Richiardi, P. Eur. J. Immunogenet. (2001) [Pubmed]
  16. Downregulation and/or release of NKG2D ligands as immune evasion strategy of human neuroblastoma. Raffaghello, L., Prigione, I., Airoldi, I., Camoriano, M., Levreri, I., Gambini, C., Pende, D., Steinle, A., Ferrone, S., Pistoia, V. Neoplasia (2004) [Pubmed]
  17. MIC expression in renal and pancreatic allografts. Hankey, K.G., Drachenberg, C.B., Papadimitriou, J.C., Klassen, D.K., Philosophe, B., Bartlett, S.T., Groh, V., Spies, T., Mann, D.L. Transplantation (2002) [Pubmed]
  18. Oxidative stress increases MICA and MICB gene expression in the human colon carcinoma cell line (CaCo-2). Yamamoto, K., Fujiyama, Y., Andoh, A., Bamba, T., Okabe, H. Biochim. Biophys. Acta (2001) [Pubmed]
  19. Interactions of human NKG2D with its ligands MICA, MICB, and homologs of the mouse RAE-1 protein family. Steinle, A., Li, P., Morris, D.L., Groh, V., Lanier, L.L., Strong, R.K., Spies, T. Immunogenetics (2001) [Pubmed]
  20. MICA, MICB and C1_4_1 polymorphism in Crohn's disease and ulcerative colitis. Glas, J., Martin, K., Brünnler, G., Kopp, R., Folwaczny, C., Weiss, E.H., Albert, E.D. Tissue Antigens (2001) [Pubmed]
  21. Transfer of NKG2D and MICB at the cytotoxic NK cell immune synapse correlates with a reduction in NK cell cytotoxic function. Roda-Navarro, P., Vales-Gomez, M., Chisholm, S.E., Reyburn, H.T. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  22. TGF-beta and metalloproteinases differentially suppress NKG2D ligand surface expression on malignant glioma cells. Eisele, G., Wischhusen, J., Mittelbronn, M., Meyermann, R., Waldhauer, I., Steinle, A., Weller, M., Friese, M.A. Brain (2006) [Pubmed]
  23. The association between non-melanoma skin cancer and a young dimorphic Alu element within the major histocompatibility complex class I genomic region. Dunn, D.S., Inoko, H., Kulski, J.K. Tissue Antigens (2006) [Pubmed]
  24. Functional expression and release of ligands for the activating immunoreceptor NKG2D in leukemia. Salih, H.R., Antropius, H., Gieseke, F., Lutz, S.Z., Kanz, L., Rammensee, H.G., Steinle, A. Blood (2003) [Pubmed]
  25. Expression of MHC Class I-Related Chain B (MICB) Molecules on Renal Transplant Biopsies. Quiroga, I., Salio, M., Koo, D.D., Cerundolo, L., Shepherd, D., Cerundolo, V., Fuggle, S.V. Transplantation (2006) [Pubmed]
  26. Association of MHC class I related gene B (MICB) to celiac disease. González, S., Rodrigo, L., López-Vázquez, A., Fuentes, D., Agudo-Ibáñez, L., Rodríguez-Rodero, S., Fdez-Morera, J.L., Martínez-Borra, J., López-Larrea, C. Am. J. Gastroenterol. (2004) [Pubmed]
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