Alternative titles; symbols
HGNC Approved Gene Symbol: TNFRSF17
Cytogenetic location: 16p13.13 Genomic coordinates (GRCh38): 16:11,965,210-11,968,068 (from NCBI)
Laabi et al. (1992) found that a t(4;16)(q26;p13.1) translocation, found in tumor cells of a patient with intestinal T-cell lymphoma, resulted in a rearrangement of the interleukin-2 gene (IL2; 147680), normally located on 4q26, with sequences from 16p13.1. Use of an IL2-specific probe to screen a cDNA library of tumor cells, Laabi et al. (1992) isolated clones that consisted, from 5-prime to 3-prime, of the 3 first exons of the IL2 gene, followed by a 16p13 in-frame sequence encoding 181 amino acids. A probe derived from this sequence detected a 1.2-kb transcript in various cell lines exhibiting mature B lymphoid cell features, but this sequence was not detected in other cell lines representative of other hematopoietic lineages, or in other organs. For this reason, the novel gene was termed BCM for B-cell maturation. The open reading frame of normal BCM cDNA predicted a 184-amino acid protein with a single transmembrane domain that had no homology with any protein sequences stored in data banks. Data indicated that the expression of BCM coincides with B-cell terminal maturation.
Using an expression cloning approach, Gross et al. (2000) identified BAFF (603969) as a ligand for BCMA.
Gras et al. (1995) found that in a myeloma cell line, BCMA is primarily expressed in a perinuclear Golgi-like structure. By transfection of kidney and B-cell lines and flow cytometry and immunofluorescence analysis, Hatzoglou et al. (2000) demonstrated that in addition to the intracytoplasmic localization, BCMA is present on the cell surface. Western blot analysis showed that overexpressed BCMA, like other TNFRs, induces activation of NFKB (164011) as well as the MAPK substrate ELK1 (311040) and the MAPKs JNK (MAPK8; 601158) and p38 (MAPK14; 600289), but not ERK (600997), via its cytoplasmic tail (residues 119 to 143). Cotransfection, immunoprecipitation, and immunoblot analysis indicated that BCMA, again through its cytoplasmic tail, associates with TRAF1 (601711), TRAF2 (601895), and TRAF3 (601896), but not with TRAF5 (602356), suggesting that these adaptor proteins further propagate signals elicited by TNFRs such as BCMA.
Querec et al. (2009) noted that a major challenge of vaccinology is to prospectively determine efficacy. They applied a systems biology approach, including multiplex cytokine analysis, flow cytometry, and microarray transcriptional profiling, to identify early gene signatures predicting immune responses in humans immunized with YF-17D, the well-established and successful vaccine for yellow fever. Computational analysis identified a gene signature that included C1QB (120570) and EIF2AK4 (609280), a part of the integrated stress response, that correlated with and predicted CD8 (see 186910)-positive T-cell responses to the vaccine. Neutralizing antibody responses completely correlated with induction of TNFRSF17. Querec et al. (2009) concluded that systems biology approaches can identify correlates of innate immunity and subsequent adaptive immune responses.
The patient from whose tumor cells the 4;16 translocation was derived (Laabi et al., 1992) had a chronic intestinal malabsorption syndrome. Histologic and immunohistochemical studies demonstrated a lymphoproliferative syndrome of mature T cells. Monoclonality was demonstrated by the presence of a rearranged band of the TCRB gene (see 186930).
Gras, M. P., Laabi, Y., Linares-Cruz, G., Blondel, M. O., Rigaut, J. P., Brouet, J. C., Leca, G., Haguenauer-Tsapis, R., Tsapis, A. BCMAp: an integral membrane protein in the Golgi apparatus of human mature B lymphocytes. Int. Immun. 7: 1093 only, 1995. [PubMed: 8527407] [Full Text: https://doi.org/10.1093/intimm/7.7.1093]
Gross, J. A., Johnston, J., Mudri, S., Enselman, R., Dillon, S. R., Madden, K., Xu, W., Parrish-Novak, J., Foster, D., Lofton-Day, C., Moore, M., Littau, A., Grossman, A., Haugen, H., Foley, K., Blumberg, H., Harrison, K., Kindsvogel, W., Clegg, C. H. TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease. Nature 404: 995-999, 2000. [PubMed: 10801128] [Full Text: https://doi.org/10.1038/35010115]
Hatzoglou, A., Roussel, J., Bourgeade, M.-F., Rogier, E., Madry, C., Inoue, J., Devergne, O., Tsapis, A. TNF receptor family member BCMA (B cell maturation) associates with TNF receptor-associated factor (TRAF) 1, TRAF2, and TRAF3 and activates NF-kappa-B, Elk-1, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase. J. Immun. 165: 1322-1330, 2000. [PubMed: 10903733] [Full Text: https://doi.org/10.4049/jimmunol.165.3.1322]
Laabi, Y., Gras, M. P., Carbonnel, F., Brouet, J. C., Berger, R., Larsen, C. J., Tsapis, A. A new gene, BCM, on chromosome 16 is fused to the interleukin 2 gene by a t(4;16)(q26;p13) translocation in a malignant T cell lymphoma. EMBO J. 11: 3897-3904, 1992. [PubMed: 1396583] [Full Text: https://doi.org/10.1002/j.1460-2075.1992.tb05482.x]
Querec, T. D., Akondy, R. S., Lee, E. K., Cao, W., Nakaya, H. I., Teuwen, D., Pirani, A., Gernert, K., Deng, J., Marzolf, B., Kennedy, K., Wu, H., Bennouna, S., Oluoch, H., Miller, J., Vencio, R. Z., Mulligan, M., Aderem, A., Ahmed, R., Pulendran, B. Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans. Nature Immun. 10: 116-125, 2009. [PubMed: 19029902] [Full Text: https://doi.org/10.1038/ni.1688]