Alternative titles; symbols
HGNC Approved Gene Symbol: LTB
Cytogenetic location: 6p21.33 Genomic coordinates (GRCh38): 6:31,580,558-31,582,425 (from NCBI)
Browning et al. (1993) pointed out that lymphotoxin-alpha, otherwise known as tumor necrosis factor-beta (TNFB; 153440), is present on the surface of activated T, B, and LAK cells as a complex with a 33-kD glycoprotein. Browning et al. (1993) cloned the cDNA encoding the associated protein, called lymphotoxin-beta, and showed that it is a type II membrane protein with significant homology to TNF, LT-alpha, and the ligand for the CD40 receptor (109535).
Nakamura et al. (1995) described lymphotoxin-alpha in a homotrimeric form as a soluble protein secreted by activated lymphocytes and presumed to act as a modulator in the immune response. The LT-alpha homotrimer shares its receptor with tumor necrosis factor and binds to both TNF receptor-1 (191190) and -2 (191191). Lymphotoxin-beta, also expressed by active lymphocytes, forms a heterotrimer with LT-alpha on the cell surface and anchors LT-alpha to the cell surface. This heterotrimer is assumed to take part in immunologic reactions by cell-cell contact, but it does not bind to either TNFR1 or TNFR2. A homotrimeric form of LT-beta has not been identified. Crowe et al. (1994) identified the TNF receptor-related protein as the human receptor for the LT-alpha/LT-beta heterotrimer, i.e., the LT-beta receptor. The gene for the TNFC receptor is symbolized TNFCR (600979).
Warzocha et al. (1997) isolated 2 LT-beta isoforms from mRNAs of a panel of human lymphoid cell lines and tumor tissues obtained from patients with non-Hodgkin lymphoma. The truncated LTB mRNA variant lacked 46 basepairs complementary to the complete sequence of exon 2, suggesting that both isoforms are produced by an alternative splicing mechanism. The predicted protein would be severely shortened and would lack the majority of the extracellular domain of the native molecule, thus impairing its normal complex assembly with LTA. These observations provide new insights into the molecular heterogeneity and biologic function of LTB within the tumor necrosis factor and LT ligand-receptor system.
Kruglov et al. (2013) showed that soluble lymphotoxin-alpha (LTA; 153440) produced by ROR-gamma-t-positive (see 602943) innate lymphoid cells (ILCs) controls T cell-dependent IgA induction in the lamina propria via regulation of T cell homing to the gut. By contrast, membrane-bound lymphotoxin-beta produced by ROR-gamma-t-positive ILCs is critical for T cell-independent IgA induction in the lamina propria via control of dendritic cell functions. Ablation of LTA in ROR-gamma-t-positive cells abrogated IgA production in the gut and altered microbiota composition. Kruglov et al. (2013) concluded that soluble and membrane-bound lymphotoxins produced by ILCs distinctly organize adaptive immune responses in the gut and control commensal microbiota composition.
Browning et al. (1993) found that the lymphotoxin-beta gene is located in the major histocompatibility complex region on chromosome 6p21.3 just centromeric of TNFA (191160), which in turn is just centromeric of TNFB. They found that the structures of the 3 genes are very similar; however, TNFC is transcribed from centromere to telomere, whereas the other 2 genes are transcribed in the opposite direction. Nalabolu et al. (1996) showed that LTB is flanked by B144 (LST1; 109170) and 1C7 (NCR3; 611550) on one side and IKBL (601022) and BAT1 (142560) on the other.
Cui et al. (2006) found that Ltb was an Eda (300451) target gene by comparative transcription profiling of embryonic skin during hair follicle development in wildtype mice and Tabby mice that have a defect in the Eda gene. Ltb was enriched in developing hair follicles of wildtype but not Tabby mice. In mice lacking Ltb, all 3 types of mouse hairs were formed, but they were structurally abnormal. Cui et al. (2006) concluded that Ltb regulates the form of hair in developing hair follicles and failure of Ltb activation can account for part of the Tabby phenotype.
Browning, J. L., Ngam-ek, A., Lawton, P., DeMarinis, J., Tizard, R., Chow, E. P., Hession, C., O'Brine-Greco, B., Foley, S. F., Ware, C. F. Lymphotoxin beta, a novel member of the TNF family that forms a heteromeric complex with lymphotoxin on the cell surface. Cell 72: 847-856, 1993. [PubMed: 7916655] [Full Text: https://doi.org/10.1016/0092-8674(93)90574-a]
Crowe, P. D., VanArsdale, T. L., Walter, B. N., Ware, C. F., Hession, C., Ehrenfels, B., Browning, J. L., Din, W. S., Goodwin, R. G, Smith, C. A. A lymphotoxin-beta-specific receptor. Science 264: 707-710, 1994. [PubMed: 8171323] [Full Text: https://doi.org/10.1126/science.8171323]
Cui, C.-Y., Hashimoto, T., Grivennikov, S. I., Piao, Y., Nedospasov, S. A., Schlessinger, D. Ectodysplasin regulates the lymphotoxin-beta pathway for hair differentiation. Proc. Nat. Acad. Sci. 103: 9142-9147, 2006. [PubMed: 16738056] [Full Text: https://doi.org/10.1073/pnas.0509678103]
Kruglov, A. A., Grivennikov, S. I., Kuprash, D. V., Winsauer, C., Prepens, S., Seleznik, G. M., Eberl, G., Littman, D. R., Heikenwalder, M., Tumanov, A. V., Nedospasov, S. A. Nonredundant function of soluble LT-alpha-3 produced by innate lymphoid cells in intestinal homeostasis. Science 342: 1243-1246, 2013. [PubMed: 24311691] [Full Text: https://doi.org/10.1126/science.1243364]
Nakamura, T., Tashiro, K., Nazarea, M., Nakano, T., Sasayama, S., Honjo, T. The murine lymphotoxin-beta receptor cDNA: isolation by the signal sequence trap and chromosomal mapping. Genomics 30: 312-319, 1995. [PubMed: 8586432] [Full Text: https://doi.org/10.1006/geno.1995.9872]
Nalabolu, S. R., Shukla, H., Nallur, G., Parimoo, S., Weissman, S. M. Genes in a 220-kb region spanning the TNF cluster in human MHC. Genomics 31: 215-222, 1996. [PubMed: 8824804] [Full Text: https://doi.org/10.1006/geno.1996.0034]
Warzocha, K., Renard, N., Charlot, C., Bienvenu, J., Coiffier, B., Salles, G. Identification of two lymphotoxin beta isoforms expressed in human lymphoid cell lines and non-Hodgkin's lymphomas. Biochem. Biophys. Res. Commun. 238: 273-276, 1997. [PubMed: 9299492] [Full Text: https://doi.org/10.1006/bbrc.1997.7277]