Lymphotoxin beta

Structure

Lymphotoxin-beta (LTB) is a type II membrane protein belonging to the TNF family. It forms heterotrimers with lymphotoxin-alpha, anchoring it to the cell surface. The predominant complex found on the surface of lymphocytes is the lymphotoxin-alpha 1/beta 2 complex (i.e., one molecule of alpha and two molecules of beta), which serves as the primary ligand for the lymphotoxin-beta receptor. A less common form is the lymphotoxin-alpha 2/beta 1 complex. Additionally, alternative splicing of the LTB gene results in multiple transcript variants encoding different isoforms. Notably, the lymphotoxin-beta isoform b cannot form a complex with lymphotoxin-alpha, indicating it may have functions independent of lymphotoxin-alpha.

Function

LTB plays a critical role in immune system regulation. It is an inducer of the inflammatory response and is essential for the normal development of lymphoid tissues. The membrane-bound lymphotoxin complexes mediate signaling through the lymphotoxin-beta receptor, influencing immune cell differentiation and tissue organization.

Clinical significance

The membrane-bound form of lymphotoxin has been implicated in tumorigenesis. Mice engineered to overexpress LTα or LTβ exhibit increased tumor growth and metastasis in several cancer models. However, earlier studies were limited by the use of mice lacking the entire LTα gene, making it difficult to distinguish the effects of soluble versus membrane-associated lymphotoxins.

Interactions

LTB has been shown to interact with Lymphotoxin alpha.

References

References

1. (Mar 1993). "Lymphotoxin beta, a novel member of the TNF family that forms a heteromeric complex with lymphotoxin on the cell surface". Cell.
2. (Aug 1991). "Lymphotoxin and an associated 33-kDa glycoprotein are expressed on the surface of an activated human T cell hybridoma". Journal of Immunology.
3. "Entrez Gene: LTB lymphotoxin beta (TNF superfamily, member 3)".
4. (January 2017). "TLR-signaling and proinflammatory cytokines as drivers of tumorigenesis.". Cytokine.
5. (Aug 1997). "The lymphotoxin-alpha (LTalpha) subunit is essential for the assembly, but not for the receptor specificity, of the membrane-anchored LTalpha1beta2 heterotrimeric ligand". The Journal of Biological Chemistry.
6. (Oct 1997). "Characterization of lymphotoxin-alpha beta complexes on the surface of mouse lymphocytes". Journal of Immunology.
7. (Jan 1995). "Characterization of surface lymphotoxin forms. Use of specific monoclonal antibodies and soluble receptors". Journal of Immunology.