Factor Bb

Background

Complement factor Bb operates within the alternative complement activation pathway. As a single-chain polypeptide, factor B cleaves by complement factor D upon pathway activation, generating the non-catalytic Ba chain and the catalytic Bb subunit. The serine protease Bb binds to C3b, assembling the alternative pathway C3 convertase. It contributes to the proliferation of preactivated B lymphocytes.

Its Gene ID: 629, UniProtKB ID: P00751, and OMIM ID: 138470.

Role of Factor Bb in Complement Activation Pathways

Factor Bb, derived from complement factor B upon activation of the alternative pathway, is generated through the enzymatic action of factor D on purified factor B from normal human serum. This process leads to the Ba fragment's release and the Bb fragment's subsequent binding to C3b. Located at the C-terminal end of factor B, Bb contains the active site of the serine protease within the C3bBb complex. Acting as both a C3 and C5 convertase, C3bBb converts C3 and C5 into their active forms by cleaving off the C3a and C5a peptides, functioning as an unstable trypsin-like serine protease with a short half-life of about 90 seconds, and rapidly dissociates in the presence of decay-accelerating factors. Upon dissociation from C3b, the Bb fragment loses its complement activity and lacks a conventional serine protease active site structure.

Fig.1 Factor Bb in complement cascade pathways.¹

Functional Roles of Factor Bb and Utilization of Bb-based Products

Factor Bb fragments have been implicated in various biological responses. Studies indicate that Bb induces activation and spreading of human and murine macrophages and monocytes, although this activity can be inhibited by anti-C5, likely by blocking secondary C5 activation and C5a release. Recent findings also highlight Bb's role in inducing apoptosis in leukemic cells and promoting survival of human endothelial cells in culture, previously attributed to a factor from fetal bovine serum. Despite possessing the proteolytic site of C3bBb, Bb lacks proteolytic activity towards C3 or C5 once dissociated from C3b, with reported low-level activity potentially attributed to thrombin contamination in some preparations.

Factor Bb as a Prognostic Biomarker in Aortic Stenosis

Inflammation is crucial in the progression of aortic stenosis (AS). Elevated circulating complement factor B levels, a critical alternative pathway component, may predict outcomes in severe symptomatic AS patients. Plasma levels of the terminal complement complex, factor B, and Bb are quantified in patients with mild-to-moderate or severe asymptomatic AS, severe symptomatic AS, and healthy controls using enzyme immunoassays with anti-Bb and anti-factor B antibodies. Symptomatic AS patients exhibit markedly elevated factor B levels compared to controls, with an inverse correlation between factor B levels and valve area observed in asymptomatic patients. High factor B levels are associated with mortality, suggesting factor B involvement from early disease stages. Elevated Bb levels show a similar mortality pattern.

Creative Biolabs offers a wide array of products focused on complement factor Bb, encompassing assay kits, recombinant proteins, and antibodies targeting Bb. Additionally, our services include custom development of Bb-specific products, such as personalized bispecific antibody solutions tailored to meet specific needs and requirements.

Factor Bb Functional Service

Creative Biolabs presents a comprehensive array of Factor Bb-related offerings, featuring anti-Factor Bb antibodies and human complement Factor Bb proteins. These products excel in detecting and tracking the interactions between antibody regions and human Factor Bb protein, serving as indispensable resources in studies aimed at therapeutic disease interventions.

Dense deposit disease (DDD) is an uncommon kidney disorder associated with the dysregulation of the alternative complement pathway. Autoantibodies targeting the C3bBb convertase, known as C3 nephritic factor, are prevalent in DDD. Researchers document a DDD patient negative for C3 nephritic factor but possessing an autoantibody binding complement factor Bb. Patient plasma underwent incubation with factor B or C3 before being applied to wells coated with factor B, or alternatively, the immobilized factor B was preincubated with goat antibodies specific to factor B and factor H, in conjunction with anti-Ba or anti-Bb monoclonal antibodies, before the patient plasma was introduced to the wells. Plasma factor B levels were quantified via ELISA, employing anti-Bb monoclonal antibody for capture and polyclonal anti-factor B for detection. This autoantibody targets the Bb fragment epitope, stabilizing the C3bBb convertase against decay, increasing C3 consumption, and inhibiting C5 convertase and terminal pathway-mediated lysis in vitro. Antigen arrays confirmed anti-factor Bb and complement-activating anti-C1q antibodies in plasma.

Creative Biolabs presents specialized solutions tailored to the investigation of factor Bb functionality, incorporating the assessment of interaction dynamics and a range of functional analyses. These services are meticulously crafted to accommodate the distinct demands of prestigious clients engaged in the realms of clinical and scientific research.

Reference

1. Shahini, Negar, et al. "The alternative complement pathway is dysregulated in patients with chronic heart failure." Scientific reports 7.1 (2017): 42532. Distributed under Open Access license CC BY 4.0, without modification.