CD59b

Background

The complement system is essential for innate immunity and plays a regulatory role in adaptive immunity. It eliminates pathogens via the membrane attack complex (MAC) or C5b-9n complex, which assembles on target surfaces for direct lysis. CD59, a membrane-bound complement regulator, restricts MAC assembly to protect host cells from bystander MAC damage. Humans have a single CD59 gene, ubiquitously expressed across most cells and tissues, while mice have two genes, mCd59a and mCd59b. mCd59b, selectively expressed in the testis and on sperm, exhibits similar or greater inhibitory efficacy than mCd59a and may also play complement-independent roles in acrosome activation and motility. Reduced mCd59a and mCd59b expression is linked to immune and inflammatory conditions like transplant rejection, autoimmune hemocytopenia, systemic lupus erythematosus, and atherosclerosis.

Its Gene ID: 333883, UniProtKB ID: P58019.

CD59b Related Pathway

Upon encountering pathogens or damaged/infected self-cells, the complement system is activated by recognizing specific surface patterns. This activation can proceed through one of three pathways: the alternative pathway (AP), the classical pathway (CP), or the lectin pathway (LP). CP is initiated by antigen-antibody complexes binding to the C1q-C1r-C1s complex. LP is activated by mannose-binding lectin attaching to pathogen surface carbohydrates and PAMPs. AP responds to cellular damage through spontaneous hydrolysis of C3 or properdin-stimulated C3 activation. The C5b fragment and C6-C9 components form the MAC that inserts into the pathogen membrane, creating a pore and causing cell lysis. C3a and C5a promote phagocytosis, immune cell chemotaxis, and immunomodulation by binding to G-protein coupled receptors. CD59b, as a membrane-anchored complement, is a regulator that closely monitors and modulates complement activation and propagation.

Fig.1 Structure of CD59b.Distributed under public domain, from Wiki, without modification.

Role of CD59b in Pancreatic Insulin Secretion

Human pancreatic islets express CD59 at high levels, yet the interaction between cell-surface CD59 and intracellular exocytotic mechanisms remains unexplored. Researchers have discovered CD59 splice variants in human pancreatic islets characterized by distinct C-terminal domains that substitute the GPI-anchoring signal. Named IRIS-1 and IRIS-2, these variants reside within the cytosol of β-cells, where they co-localize with insulin granules and promote insulin secretion without CD59. Notably, IRIS-1 and IRIS-2 expression is markedly reduced in pancreatic islets from type 2 diabetes patients compared to healthy controls, implicating them in insulin deficiency under hyperglycemic conditions. Similarly, mouse CD59b exhibits tissue-specific expression prominently in pancreatic islets, and its expression is down-regulated in diabetic Akita mouse islets. These findings underscore the critical role of CD59b variants in pancreatic function and insulin secretion.

Creative Biolabs provides an extensive selection of CD59b-targeted products, including assay kits, recombinant proteins, and anti-CD59b antibodies. Furthermore, we offer custom services to develop CD59b-specific products tailored to precise individual requirements.

CD59b Functional Service

Creative Biolabs offers an extensive array of CD59b-related products, including recombinant CD59b proteins. These meticulously engineered tools are intended to accurately detect and track interactions involving the human CD59b protein and various other molecules. Serving as vital resources, they support research focused on developing innovative therapeutic strategies across diverse disease areas.

CD59, an essential membrane complement regulatory protein, inhibits membrane attack complex formation to shield host cells from complement-mediated damage. Researchers have identified Sp1 as a key regulator of constitutive CD59 transcription, while canonical NF-κB and CREB oversee inducible CD59 transcription. However, mCd59 regulation mechanisms differ. Western-blot results shown that Sp1 governs mCd59a broadly, whereas mCd59b expression is modulated by SRF and NF-κB, particularly in response to external inflammatory signals like TNF-α and lipopolysaccharide, suggesting mCd59b’s prominent role in inflammatory responses.

Creative Biolabs offers expert services centered on CD59b function, including the analysis of CD59b-binding interactions and additional functional evaluations. These services are meticulously crafted to fulfill the unique needs of distinguished clients involved in clinical and research fields.