Disease relevance of MICB

• The human cytomegalovirus glycoprotein, UL16, binds to two members of a novel family of molecules, the ULBPs, and to the MHC class I homolog, MICB [1].
• Expression and role of MICA and MICB in human hepatocellular carcinomas and their regulation by retinoic acid [2].
• Eight novel MICB alleles, including a null allele, identified in gastric MALT lymphoma patients [3].
• MICA rather than MICB, TNFA, or HLA-DRB1 is associated with susceptibility to psoriatic arthritis [4].
• Because PSC is strongly associated with inflammatory bowel disease, we investigated whether MICA and MICB contribute to the HLA-associated genetic susceptibility to develop PSC [5].

High impact information on MICB

• Ligands of NKG2D include the major histocompatibility complex class I homologues MICA and MICB, which function as signals of cellular stress [6].
• MICA and the closely related MICB were recognized by intestinal epithelial T cells expressing diverse Vdelta1 gammadelta TCRs [7].
• With intestinal epithelial cell lines, the expression and recognition of MICA and MICB could be stress-induced [7].
• These interactions involved the alpha1alpha2 domains of MICA and MICB but were independent of antigen processing [7].
• UL16 is retained in the endoplasmic reticulum and cis-Golgi apparatus of cells and causes MICB to be similarly retained and stabilized within cells [8].

Biological context of MICB

• Here, NK susceptibility of myeloma cells derived from distinct disease stages was evaluated in relation to major histocompatibility complex (MHC) class I, MHC class I chain-related protein A (MICA), MHC class I chain-related protein B (MICB), and UL16 binding protein (ULBP) expression [9].
• We report that the UL16-MICB interaction is independent of glycosylation and demonstrate that selective MICB recognition by UL16 is governed by helical structures of the MICB alpha2 domain [10].
• The two segments of approximately 35 kb upstream of the MICA and MICB genes showed high sequence homology (about 85%) to each other, suggesting that segmental genome duplication including the MICA and MICB genes must have occurred during the evolution of the human MHC [11].
• Study on the haplotypes of MICA and MICB microsatellite and HLA-B locus in the Guangzhou Han population [12].
• In total, five alleles of MICA microsatellite locus and 14 alleles of MICB microsatellite locus were observed [12].

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

• The novel MICB null allele is characterized by a Cytosin (C) deletion in a stretch of four Cs beginning from nucleotide 135 of exon 2 that leads to a premature stop codon (TGA) at codon 66 [3].
• MICA and MICB genes are found in the class I region between HLA-B and DRB [5].
• METHODS: A monoclonal antibody directed against MICA and MICB was used to perform indirect immunohistochemistry on formalin fixed, paraffin embedded needle biopsies of kidney and pancreas allografts [17].
• We demonstrate here that oxidative stress, induced by H(2)O(2), promoted MICA (2.2-fold) and MICB (3.8-fold) gene expression using the human colon carcinoma cell line (CaCo-2) and semi-quantitative RT-PCR [18].

Physical interactions of MICB

• Soluble NKG2D also bound to cell surface MICB, which has structural and functional properties similar to those of MICA [19].
• MICA and MICB belong to a multicopy gene family located in the major histocompatibility complex (MHC) class I region near the HLA-B gene [20].

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].

References