complement factor b


Summary: A glycine-rich, heat-labile serum glycoprotein that contains a component of the C3 CONVERTASE ALTERNATE PATHWAY (C3bBb). Bb, a serine protease, is generated when factor B is cleaved by COMPLEMENT FACTOR D into Ba and Bb.

Top Publications

  1. Spencer K, Hauser M, Olson L, Schmidt S, Scott W, Gallins P, et al. Protective effect of complement factor B and complement component 2 variants in age-related macular degeneration. Hum Mol Genet. 2007;16:1986-92 pubmed
    ..21, 95% confidence interval 0.11-0.39; P < 10(-4)). Likelihood ratio testing and conditional analyses in the case-control data set suggest that a weaker, independent protective effect exists for CC2 E318D. ..
  2. Thakkinstian A, McEvoy M, Chakravarthy U, Chakrabarti S, McKay G, Ryu E, et al. The association between complement component 2/complement factor B polymorphisms and age-related macular degeneration: a HuGE review and meta-analysis. Am J Epidemiol. 2012;176:361-72 pubmed publisher
    The authors performed a systematic review of the association of complement component 2(C2)/complement factor B (CFB) gene polymorphisms with age-related macular degeneration (AMD)...
  3. Heurich M, Martinez Barricarte R, Francis N, Roberts D, Rodriguez de Cordoba S, Morgan B, et al. Common polymorphisms in C3, factor B, and factor H collaborate to determine systemic complement activity and disease risk. Proc Natl Acad Sci U S A. 2011;108:8761-6 pubmed publisher
    ..0001). These data introduce the concept of a functional complotype (combination of polymorphisms) defining complement activity in an individual, thereby influencing susceptibility to AP-driven disease. ..
  4. Singh M, Kapoun A, Higgins L, Kutschke W, Thurman J, Zhang R, et al. Ca2+/calmodulin-dependent kinase II triggers cell membrane injury by inducing complement factor B gene expression in the mouse heart. J Clin Invest. 2009;119:986-96 pubmed publisher
    ..We studied 1 of these proinflammatory genes, complement factor B (Cfb), in detail, because complement proteins secreted by cells other than cardiomyocytes can induce ..
  5. Tortajada A, Montes T, Martinez Barricarte R, Morgan B, Harris C, de Cordoba S. The disease-protective complement factor H allotypic variant Ile62 shows increased binding affinity for C3b and enhanced cofactor activity. Hum Mol Genet. 2009;18:3452-61 pubmed publisher
  6. Liu X, Zhao P, Tang S, Lu F, Hu J, Lei C, et al. Association study of complement factor H, C2, CFB, and C3 and age-related macular degeneration in a Han Chinese population. Retina. 2010;30:1177-84 pubmed publisher
  7. Nataf S, Carroll S, Wetsel R, Szalai A, Barnum S. Attenuation of experimental autoimmune demyelination in complement-deficient mice. J Immunol. 2000;165:5867-73 pubmed
    ..These results suggest that complement might be a target for the therapeutic treatment of inflammatory demyelinating diseases of the CNS. ..
  8. Leinhase I, Holers V, Thurman J, Harhausen D, Schmidt O, Pietzcker M, et al. Reduced neuronal cell death after experimental brain injury in mice lacking a functional alternative pathway of complement activation. BMC Neurosci. 2006;7:55 pubmed
    ..Pharmacological targeting of the alternative complement pathway during the "time-window of opportunity" after TBI may represent a promising new strategy to be pursued in future studies. ..
  9. Goicoechea de Jorge E, Harris C, Esparza Gordillo J, Carreras L, Arranz E, Garrido C, et al. Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome. Proc Natl Acad Sci U S A. 2007;104:240-5 pubmed

More Information


  1. Seeger A, Mayer W, Klein J. A complement factor B-like cDNA clone from the zebrafish (Brachydanio rerio). Mol Immunol. 1996;33:511-20 pubmed
    ..After the duplication, the C2 component evolved significantly faster than factor B. ..
  2. Hourcade D, Mitchell L, Oglesby T. Mutations of the type A domain of complement factor B that promote high-affinity C3b-binding. J Immunol. 1999;162:2906-11 pubmed
  3. Nakao M, Fushitani Y, Fujiki K, Nonaka M, Yano T. Two diverged complement factor B/C2-like cDNA sequences from a teleost, the common carp (Cyprinus carpio). J Immunol. 1998;161:4811-8 pubmed
    ..A possible phylogenetic relationship between the two carp sequences and mammalian C2 and B is discussed...
  4. Kirkitadze M, Barlow P. Structure and flexibility of the multiple domain proteins that regulate complement activation. Immunol Rev. 2001;180:146-61 pubmed
    ..The results could have implications for folding, evolution, flexibility and structure-function relationships of other molecules in the large, diverse and little understood category of multiple domain proteins. ..
  5. Peake P, Kriketos A, Campbell L, Charlesworth J. Response of the alternative complement pathway to an oral fat load in first-degree relatives of subjects with type II diabetes. Int J Obes (Lond). 2005;29:429-35 pubmed
    ..These data do not support an essential requirement of the hypothesis that ASP is produced in response to the intake of fat. ..
  6. Banda N, Thurman J, Kraus D, Wood A, Carroll M, Arend W, et al. Alternative complement pathway activation is essential for inflammation and joint destruction in the passive transfer model of collagen-induced arthritis. J Immunol. 2006;177:1904-12 pubmed
    ..The mechanisms by which these target organ-specific mAbs bypass the requirements for engagement of the classical pathway remain to be defined but do not appear to involve a lack of alternative pathway regulatory proteins. ..
  7. Smith L, Clow L, Terwilliger D. The ancestral complement system in sea urchins. Immunol Rev. 2001;180:16-34 pubmed
  8. Forneris F, Ricklin D, Wu J, Tzekou A, Wallace R, Lambris J, et al. Structures of C3b in complex with factors B and D give insight into complement convertase formation. Science. 2010;330:1816-20 pubmed publisher
    ..This concerted proteolytic mechanism, which is cofactor-dependent and substrate-induced, restricts complement amplification to C3b-tagged target cells. ..
  9. Goring K, Huang Y, Mowat C, Leger C, Lim T, Zaheer R, et al. Mechanisms of human complement factor B induction in sepsis and inhibition by activated protein C. Am J Physiol Cell Physiol. 2009;296:C1140-50 pubmed publisher
    To investigate the potential role of the local expression of alternative complement factor B (hBf) in human sepsis, we examined the induction of Bf gene expression in human peripheral blood monocytes (PBMCs) from patients with septic ..
  10. Yoshizaki F, Ikawa S, Satake M, Satoh N, Nonaka M. Structure and the evolutionary implication of the triplicated complement factor B genes of a urochordate ascidian, Ciona intestinalis. Immunogenetics. 2005;56:930-42 pubmed publisher
    To elucidate the evolution of the complement system and MHC class III region, we analyzed the complement factor B (Bf) genes of a urochordate ascidian, Ciona intestinalis...
  11. Milder F, Gomes L, Schouten A, Janssen B, Huizinga E, Romijn R, et al. Factor B structure provides insights into activation of the central protease of the complement system. Nat Struct Mol Biol. 2007;14:224-8 pubmed
    ..This allosteric mechanism is crucial for tight regulation of the complement-amplification step in the immune response. ..
  12. He Y, Tang B, Zhang S, Liu Z, Zhao B, Chen L. Molecular and immunochemical demonstration of a novel member of Bf/C2 homolog in amphioxus Branchiostoma belcheri: implications for involvement of hepatic cecum in acute phase response. Fish Shellfish Immunol. 2008;24:768-78 pubmed publisher
  13. Kavanagh D, Kemp E, Richards A, Burgess R, Mayland E, Goodship J, et al. Does complement factor B have a role in the pathogenesis of atypical HUS?. Mol Immunol. 2006;43:856-9 pubmed
    Atypical haemolytic uraemic syndrome (aHUS) is a disorder of complement dysregulation. Because complement factor B (fB) carries the catalytic site of the alternative pathway convertase we examined it as both a potential candidate gene ..
  14. Wang J, Ohno Matsui K, Yoshida T, Shimada N, Ichinose S, Sato T, et al. Amyloid-beta up-regulates complement factor B in retinal pigment epithelial cells through cytokines released from recruited macrophages/microglia: Another mechanism of complement activation in age-related macular degeneration. J Cell Physiol. 2009;220:119-28 pubmed publisher
  15. Thurman J, Kraus D, Girardi G, Hourcade D, Kang H, Royer P, et al. A novel inhibitor of the alternative complement pathway prevents antiphospholipid antibody-induced pregnancy loss in mice. Mol Immunol. 2005;42:87-97 pubmed
    ..The mAb protects mice in an in vivo model of antiphospholipid antibody syndrome, demonstrating the therapeutic potential for the inhibition of factor B in this disease. ..
  16. Lee K, Vithana E, Mathur R, Yong V, Yeo I, Thalamuthu A, et al. Association analysis of CFH, C2, BF, and HTRA1 gene polymorphisms in Chinese patients with polypoidal choroidal vasculopathy. Invest Ophthalmol Vis Sci. 2008;49:2613-9 pubmed publisher
    ..Variants in the C2 and BF genes have been found to confer a significantly reduced risk of AMD. This study was undertaken to determine whether these associations occur in Chinese patients with PCV...
  17. Huang Y, Krein P, Muruve D, Winston B. Complement factor B gene regulation: synergistic effects of TNF-alpha and IFN-gamma in macrophages. J Immunol. 2002;169:2627-35 pubmed
    b>Complement factor B (Bf) plays an important role in activating the alternative complement pathway. The inflammatory cytokines, in particular TNF-alpha and IFN-gamma, are critical in the regulation of Bf gene expression in macrophages...
  18. Le G, Abbenante G, Fairlie D. Profiling the enzymatic properties and inhibition of human complement factor B. J Biol Chem. 2007;282:34809-16 pubmed
    Human complement factor B is the crucial catalytic component of the C3 convertase enzyme that activates the alternative pathway of complement-mediated immunity...
  19. Robson M, Cook H, Botto M, Taylor P, Busso N, Salvi R, et al. Accelerated nephrotoxic nephritis is exacerbated in C1q-deficient mice. J Immunol. 2001;166:6820-8 pubmed
    ..The increased IgG deposits and apoptotic cells in the glomeruli of C1q-deficient mice suggest that the exacerbation of disease may be due to a defect in the clearance of immune complexes and/or apoptotic cells from their kidneys. ..
  20. Harris C, Pettigrew D, Lea S, Morgan B. Decay-accelerating factor must bind both components of the complement alternative pathway C3 convertase to mediate efficient decay. J Immunol. 2007;178:352-9 pubmed
    ..These data provide new insights into the mechanisms involved in C3 convertase decay by DAF. ..
  21. Tawadrous H, Maga T, Sharma J, Kupferman J, Smith R, Schoeneman M. A novel mutation in the complement factor B gene (CFB) and atypical hemolytic uremic syndrome. Pediatr Nephrol. 2010;25:947-51 pubmed publisher
    We report the case of an 8-year-old girl diagnosed with atypical hemolytic uremic syndrome (aHUS) with a complement factor B (CFB) gene mutation. aHUS is a disease of complement dysregulation...
  22. Kato Y, Salter Cid L, Flajnik M, Kasahara M, Namikawa C, Sasaki M, et al. Isolation of the Xenopus complement factor B complementary DNA and linkage of the gene to the frog MHC. J Immunol. 1994;153:4546-54 pubmed
  23. Pinto M, Melillo D, Giacomelli S, Sfyroera G, Lambris J. Ancient origin of the complement system: emerging invertebrate models. Adv Exp Med Biol. 2007;598:372-88 pubmed
  24. Chen M, Muckersie E, Robertson M, Forrester J, Xu H. Up-regulation of complement factor B in retinal pigment epithelial cells is accompanied by complement activation in the aged retina. Exp Eye Res. 2008;87:543-50 pubmed publisher
    ..Here we investigated the production and regulation of complement factor B (CFB) in RPE cells...
  25. Cianflone K, Xia Z, Chen L. Critical review of acylation-stimulating protein physiology in humans and rodents. Biochim Biophys Acta. 2003;1609:127-43 pubmed
    ..The aim of the present review is to provide a comprehensive overview of the recent literature on ASP, with particular emphasis on those studies carried out in rodents and humans. ..
  26. Gros P, Milder F, Janssen B. Complement driven by conformational changes. Nat Rev Immunol. 2008;8:48-58 pubmed
    ..Insights into the mechanisms of complement amplification are crucial for understanding host defence and pathogen immune evasion, and for the development of complement-immune therapies. ..
  27. Løvoll M, Kilvik T, Boshra H, Bøgwald J, Sunyer J, Dalmo R. Maternal transfer of complement components C3-1, C3-3, C3-4, C4, C5, C7, Bf, and Df to offspring in rainbow trout (Oncorhynchus mykiss). Immunogenetics. 2006;58:168-79 pubmed
    ..This study is the first to address the ontogeny of several complement components and represents the first evidence that maternal transfer of complement components, other than C3, occurs in teleost fish. ..
  28. Hinshelwood J, Spencer D, Edwards Y, Perkins S. Identification of the C3b binding site in a recombinant vWF-A domain of complement factor B by surface-enhanced laser desorption-ionisation affinity mass spectrometry and homology modelling: implications for the activity of factor B. J Mol Biol. 1999;294:587-99 pubmed
  29. Morley B, Campbell R. Internal homologies of the Ba fragment from human complement component Factor B, a class III MHC antigen. EMBO J. 1984;3:153-7 pubmed
    ..6 kb in length. ..
  30. Held K, Thiel S, Loos M, Petry F. Increased susceptibility of complement factor B/C2 double knockout mice and mannan-binding lectin knockout mice to systemic infection with Candida albicans. Mol Immunol. 2008;45:3934-41 pubmed publisher
    ..We investigated the susceptibility of mice deficient in complement factor B and C2 (Bf/C2-/-), C1q (C1qa-/-), and mannan-binding lectin (MBL)-A (MBL-A) and MBL-C (MBL-A/C-/-) to ..
  31. Kumar N, Kaur G, Tandon N, Mehra N. Allotyping human complement factor B in Asian Indian type 1 diabetic patients. Tissue Antigens. 2008;72:517-24 pubmed publisher
    Human complement factor B (BF) is an essential component of the alternate complement pathway and therefore important in innate immune and autoimmune responses...
  32. Kristensen T, Tack B. Murine protein H is comprised of 20 repeating units, 61 amino acids in length. Proc Natl Acad Sci U S A. 1986;83:3963-7 pubmed
    ..Similar repetitive units are present in the C4b binding protein, the C3b-receptor (CR1), complement factor B and C2, and in beta 2-glycoprotein I and the interleukin 2 receptor...
  33. Xia Z, Cianflone K. Acylation-stimulating protein precursor proteins in adipose tissue in human obesity. Metabolism. 2003;52:1360-6 pubmed
    ..In males, there is increased expression in OM tissue. In addition, relative OM/SC expression increases with obesity and these changes may contribute to the development of visceral adipose tissue. ..
  34. Jing H, Xu Y, Carson M, Moore D, Macon K, Volanakis J, et al. New structural motifs on the chymotrypsin fold and their potential roles in complement factor B. EMBO J. 2000;19:164-73 pubmed
    ..The bottom of the S1 pocket has a negative charge at residue 226 instead of the typical 189 position. These unique structural features may play different roles in domain-domain interaction, cofactor binding and substrate binding. ..
  35. Zou L, Feng Y, Li Y, Zhang M, Chen C, Cai J, et al. Complement factor B is the downstream effector of TLRs and plays an important role in a mouse model of severe sepsis. J Immunol. 2013;191:5625-35 pubmed publisher
    ..In this article, we show that activation of TLR2, TLR3, and TLR4 markedly enhanced complement factor B (cfB) synthesis and release by macrophages and cardiac cells...
  36. Hughes A, Mullan G, Bradley D. Complement factor B polymorphism 32W protects against age-related macular degeneration. Mol Vis. 2011;17:983-8 pubmed
    The 32Q (rs641153; A) and 32W (rs12614; T) variants of complement factor B (CFB) cause less efficient complement activation in vitro than the common 32R variant...
  37. Matsumoto M, Fukuda W, Circolo A, Goellner J, Strauss Schoenberger J, Wang X, et al. Abrogation of the alternative complement pathway by targeted deletion of murine factor B. Proc Natl Acad Sci U S A. 1997;94:8720-5 pubmed
    ..Nevertheless, these mice provide an excellent model for the assessment of the role of Bf and the alternative pathway in host defense and other functions in vivo. ..
  38. Kapadia S, Levine B, Speck S, Virgin H. Critical role of complement and viral evasion of complement in acute, persistent, and latent gamma-herpesvirus infection. Immunity. 2002;17:143-55 pubmed
  39. Paglialunga S, Fisette A, Yan Y, Deshaies Y, Brouillette J, Pekna M, et al. Acylation-stimulating protein deficiency and altered adipose tissue in alternative complement pathway knockout mice. Am J Physiol Endocrinol Metab. 2008;294:E521-9 pubmed
    ..Mice lacking alternative complement factor B or adipsin (FBKO or ADKO), required for ASP production, were also ASP deficient...
  40. Thurman J, Royer P, Ljubanovic D, Dursun B, Lenderink A, Edelstein C, et al. Treatment with an inhibitory monoclonal antibody to mouse factor B protects mice from induction of apoptosis and renal ischemia/reperfusion injury. J Am Soc Nephrol. 2006;17:707-15 pubmed
    ..Thus, use of an inhibitory mAb to mouse factor B effectively prevented activation of complement in the kidney after I/R and protected the mice from necrotic and apoptotic injury of the tubules. ..
  41. Seddon J, Reynolds R, Maller J, Fagerness J, Daly M, Rosner B. Prediction model for prevalence and incidence of advanced age-related macular degeneration based on genetic, demographic, and environmental variables. Invest Ophthalmol Vis Sci. 2009;50:2044-53 pubmed publisher
    ..831 for progression to advanced AMD. Factors reflective of nature and nurture are independently related to prevalence and incidence of advanced AMD, with excellent predictive power. ..
  42. Thurman J, Ljubanovic D, Edelstein C, Gilkeson G, Holers V. Lack of a functional alternative complement pathway ameliorates ischemic acute renal failure in mice. J Immunol. 2003;170:1517-23 pubmed
    ..that complement activation in this setting occurs via the alternative pathway and that mice deficient in complement factor B, an essential component of the alternative pathway, would be protected from ischemic ARF...
  43. Xu Y, Ma M, Ippolito G, Schroeder H, Carroll M, Volanakis J. Complement activation in factor D-deficient mice. Proc Natl Acad Sci U S A. 2001;98:14577-82 pubmed
    ..Kinetics of opsonization of Streptococcus pneumoniae by C3 fragments was much slower in factor D-deficient serum, suggesting a significant contribution of the alternative pathway to antibacterial host defense early after infection. ..
  44. Wu X, Spitzer D, Mao D, Peng S, Molina H, Atkinson J. Membrane protein Crry maintains homeostasis of the complement system. J Immunol. 2008;181:2732-40 pubmed
    ..They imply that there is constant turnover on cells of the AP pathway which functions as an immune surveillance system for pathogens and altered self. ..
  45. Rainard P. Complement factor B and the alternative pathway of complement activation in bovine milk. J Dairy Res. 2002;69:1-12 pubmed
    ..Heating at 56 degrees C for at least 45 min was necessary to completely inhibit C3 deposition in normal milk. ..
  46. Taylor P, Nash J, Theodoridis E, Bygrave A, Walport M, Botto M. A targeted disruption of the murine complement factor B gene resulting in loss of expression of three genes in close proximity, factor B, C2, and D17H6S45. J Biol Chem. 1998;273:1699-704 pubmed
    ..The resulting mouse is deficient in both factor B and C2, and hence the alternative and classical pathways of complement activation, and adds to the repertoire of models for studying the in vivo role of complement in the immune system. ..
  47. Gabrielsson B, Johansson J, Lönn M, Jernas M, Olbers T, Peltonen M, et al. High expression of complement components in omental adipose tissue in obese men. Obes Res. 2003;11:699-708 pubmed
  48. Buentello Volante B, Rodriguez Ruiz G, Miranda Duarte A, Pompa Mera E, Graue Wiechers F, Bekker Mendez C, et al. Susceptibility to advanced age-related macular degeneration and alleles of complement factor H, complement factor B, complement component 2, complement component 3, and age-related maculopathy susceptibility 2 genes in a Mexican population. Mol Vis. 2012;18:2518-25 pubmed
    ..association of age-related macular degeneration (AMD)-high risk alleles of the complement factor H (CFH), complement factor B (CFB), complement component 2 (C2), complement component 3 (C3), and age-related maculopathy susceptibility ..
  49. Seriramalu R, Pang W, Jayapalan J, Mohamed E, Abdul Rahman P, Bustam A, et al. Application of champedak mannose-binding lectin in the glycoproteomic profiling of serum samples unmasks reduced expression of alpha-2 macroglobulin and complement factor B in patients with nasopharyngeal carcinoma. Electrophoresis. 2010;31:2388-95 pubmed publisher
    ..Reduced expression of alpha-2 macroglobulin (AMG) and complement factor B (CFB) was detected in sera of patients with nasopharyngeal carcinoma (NPC) when pooled serum samples of the ..
  50. Gold B, Merriam J, Zernant J, Hancox L, Taiber A, Gehrs K, et al. Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration. Nat Genet. 2006;38:458-62 pubmed
    ..These data expand and refine our understanding of the genetic risk for AMD. ..
  51. Reynolds R, Hartnett M, Atkinson J, Giclas P, Rosner B, Seddon J. Plasma complement components and activation fragments: associations with age-related macular degeneration genotypes and phenotypes. Invest Ophthalmol Vis Sci. 2009;50:5818-27 pubmed publisher
    ..C5a is associated with AMD genotypes. C statistics are stronger with the addition of C3a, Bb, and C5a in predictive models. Results implicate ongoing activation of the alternative complement pathway in AMD pathogenesis. ..
  52. Lima L, Schubert C, Ferrara D, Merriam J, Imamura Y, Freund K, et al. Three major loci involved in age-related macular degeneration are also associated with polypoidal choroidal vasculopathy. Ophthalmology. 2010;117:1567-70 pubmed publisher
    ..To investigate the frequency of variants in 3 major age-related macular degeneration (AMD)-associated loci in patients of European-American descent with polypoidal choroidal vasculopathy (PCV)...
  53. Jakobsdottir J, Conley Y, Weeks D, Ferrell R, Gorin M. C2 and CFB genes in age-related maculopathy and joint action with CFH and LOC387715 genes. PLoS ONE. 2008;3:e2199 pubmed publisher
    ..Two other complement pathway genes, the closely linked complement component receptor (C2) and complement factor B (CFB), were recently shown to harbor variants associated with ARM...