Alternative titles; symbols
HGNC Approved Gene Symbol: CD72
Cytogenetic location: 9p13.3 Genomic coordinates (GRCh38): 9:35,609,982-35,646,857 (from NCBI)
By means of monoclonal antibodies, Von Hoegen et al. (1991) demonstrated identity of CD72 to the human homolog of mouse Lyb2. Expression of Lyb2 is restricted to B-lineage cells and is turned off in antibody-secreting plasma cells in both mice and humans. The protein may be involved in signals for B-cell proliferation.
Von Hoegen et al. (1991) localized the CD72 gene to the short arm of human chromosome 9 by study of mouse/human somatic cell hybrids. The mouse Lyb2 gene had previously been mapped to chromosome 4.
In a review of immune inhibitory receptors, Ravetch and Lanier (2000) pointed out that autoimmune disorders may result from the disruption of inhibitory receptors, particularly in their conserved intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs). ITIMs are sites for alternative phosphorylation, typically by a Src kinase, and dephosphorylation, either by the tyrosine phosphatase SHP1 (176883) or the inositol phosphatase SHIP (601582), transducing signals to distinct pathways. B cells from CD72-deficient mice are hyperresponsive to lipopolysaccharide stimulation and B cell receptor aggregation.
Using a mouse model, Kumanogoh et al. (2000) determined that the CD100 (SEMA4D; 601866) receptor plexin B1 (PLXNB1; 601053) is not detectable in lymphocytes, and that in the immune system, CD72 appears to be the receptor for CD100.
Hitomi et al. (2004) tested the association of CD72 polymorphisms with systemic lupus erythematosus (SLE; 152700) and examined genetic interaction with FCGR2B (604590) in Japanese, Thai, and Caucasian cohorts. Although they did not detect association with susceptibility to SLE, the CD72 *1 allele, which contains a single 13-bp repeat in intron 8, was significantly associated with nephritis among Japanese patients. RT-PCR identified an alternatively spliced (AS) CD72 transcript that replaced 42 amino acids of the extracellular domain with 49 amino acids, caused by skipping of exon 8 and inclusion of exon 9. The ratio of AS/common isoforms was increased in individuals with *2/*2 genotype, which contains 2 13-bp repeats in intron 8, when compared with *1/*1 or *1/*2 genotypes. In the Japanese and Thai cohorts, significant association of the FCGR2B 232thr/thr genotype (604590.0002) with SLE was observed only with the CD72 *1/*1 genotype (p = 0.009). Minigene assays demonstrated that the 13-bp repeat and a 4-bp deletion within the same haplotype of intron 8 could regulate alternative splicing. Hitomi et al. (2004) concluded that the CD72 *2 allele may decrease risk for human SLE conferred by FCGR2B 232thr/thr, possibly by increasing the AS isoform of CD72.
Hitomi, Y., Tsuchiya, N., Kawasaki, A., Ohashi, J., Suzuki, T., Kyogoku, C., Fukazawa, T., Bejrachandra, S., Siriboonrit, U., Chandanayingyong, D., Suthipinittharm, P., Tsao, B. P., Hashimoto, H., Honda, Z., Tokunaga, K. CD72 polymorphisms associated with alternative splicing modify susceptibility to human systemic lupus erythematosus through epistatic interaction with FCGR2B. Hum. Molec. Genet. 13: 2907-2917, 2004. [PubMed: 15459183] [Full Text: https://doi.org/10.1093/hmg/ddh318]
Kumanogoh, A., Watanabe, C., Lee, I., Wang, X., Shi, W., Araki, H., Hirata, H., Iwahori, K., Uchida, J., Yasui, T., Matsumoto, M., Yoshida, K., Yakura, H., Pan, C., Parnes, J. R., Kikutani, H. Identification of CD72 as a lymphocyte receptor for the class IV semaphorin CD100: a novel mechanism for regulating B cell signaling. Immunity 13: 621-631, 2000. [PubMed: 11114375] [Full Text: https://doi.org/10.1016/s1074-7613(00)00062-5]
Ravetch, J. V., Lanier, L. L. Immune inhibitory receptors. Science 290: 84-89, 2000. [PubMed: 11021804] [Full Text: https://doi.org/10.1126/science.290.5489.84]
Von Hoegen, I., Hsieh, C.-L., Scharting, R., Francke, U., Parnes, J. R. Identity of human Lyb-2 and CD72 and localization of the gene to chromosome 9. Europ. J. Immun. 21: 1425-1431, 1991. [PubMed: 2044654] [Full Text: https://doi.org/10.1002/eji.1830210615]