WordNet

be a contributing factor; "make things factor into a companys profitability"
any of the numbers (or symbols) that form a product when multiplied together
an independent variable in statistics
anything that contributes causally to a result; "a number of factors determined the outcome"
consider as relevant when making a decision; "You must factor in the recent developments" (同)factor in, factor out
resolve into factors; "a quantum computer can factor the number 15" (同)factor in, factor out
small room in which a monk or nun lives (同)cubicle
a device that delivers an electric current as the result of a chemical reaction (同)electric cell
a room where a prisoner is kept (同)jail cell, prison cell
(biology) the basic structural and functional unit of all organisms; they may exist as independent units of life (as in monads) or may form colonies or tissues as in higher plants and animals
any small compartment; "the cells of a honeycomb"
a small unit serving as part of or as the nucleus of a larger political movement (同)cadre
an event known to have happened or something known to have existed; "your fears have no basis in fact"; "how much of the story is fact and how much fiction is hard to tell"
a concept whose truth can be proved; "scientific hypotheses are not facts"
a piece of information about circumstances that exist or events that have occurred; "first you must collect all the facts of the case"
a statement or assertion of verified information about something that is the case or has happened; "he supported his argument with an impressive array of facts"
the 2nd letter of the Roman alphabet (同)b
the blood group whose red cells carry the B antigen (同)type_B, group B
causing motion or action or change (同)actuating

PrepTutorEJDIC

(…の)『要因』,(…を生み出す)要素《+『in』+『名』(do『ing』)》 / 囲数,約数 / 代理人,《おもに英》仲買人 / =factorize
(刑務所の)『独房』;(修道院の)小さい独居室 / (ミツバチの)みつ房,巣穴 / 小さい部屋 / 『細胞』 / 電池 / 花粉室 / (共産党などの)細胞
〈C〉『事実』,実際にある(あった)事 / 〈U〉真相,真実(truth) / 《the~》(法律用語で)犯行

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/07/29 15:31:36」(JST)

wiki en

B-cell activating factor (BAFF) also known as tumor necrosis factor ligand superfamily member 13C is a protein that in humans is encoded by the TNFSF13C gene.^[1]^[2] BAFF is also known as B Lymphocyte Stimulator (BLyS) and TNF- and APOL-related leukocyte expressed ligand (TALL-1) and the Dendritic cell-derived TNF-like molecule (CD257 antigen; cluster of differentiation 257).

Structure and function[edit]

BAFF is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This cytokine is a ligand for receptors TNFRSF13B/TACI, TNFRSF17/BCMA, and TNFRSF13C/BAFFR. This cytokine is expressed in B cell lineage cells, and acts as a potent B cell activator. It has been also shown to play an important role in the proliferation and differentiation of B cells.^[3]

BAFF is a 285-amino acid long peptide glycoprotein which undergoes glycosylation at residue 124. It is expressed as transmembrane protein on various cell types including monocytes, dendritic cells and bone marrow stromal cells. The transmembrane form can be cleaved from the membrane, generating a soluble protein fragment. BAFF is the natural ligand of three unusual tumor necrosis factor receptors named BAFF-R, TACI, and BCMA, all of which have differing binding affinities for it. These receptors are expressed mainly on mature B lymphocytes (TACI is also found on a subset of T-cells and BCMA on plasma cells). TACI binds worst since its affinity is higher for a protein similar to BAFF, called a proliferation-inducing ligand (APRIL). BCMA displays an intermediate binding phenotype and will work with either BAFF or APRIL to varying degrees. Signaling through BAFF-R and BCMA stimulates B lymphocytes to undergo proliferation and to counter apoptosis. All these ligands act as homotrimers (i.e. three of the same molecule) interacting with homotrimeric receptors,^[4] although BAFF has been known to be active as either a hetero- or homotrimer.^[5]

Interactions[edit]

B-cell activating factor has been shown to interact with TNFRSF13B,^[6]^[7] TNFSF13^[8] and TNFRSF17.^[9]^[10]

Clinical significance[edit]

As an immunostimulant, BAFF (BLyS, TALL-1) is necessary for maintaining normal immunity. Inadequate level of BAFF will fail to activate B cells to produce enough immunoglobulin and will lead to immunodeficiency.

Human BLyS was expressed and purified in E. Coli. The BLyS protein in the engineered bacteria can be as rich as 50% to the bacteria’s total protein content and still retains activity after an easy purification procedure. Due to the ease of bacterial platform, the bacteria expressed BLyS will dramatically reduce the cost of BLyS as a potential pharmaceutical agent for immunodeficiency (http://www.ncbi.nlm.nih.gov/pubmed/14673506).

Excessive level of BAFF causes abnormally high antibody production, results in systemic lupus erythmatosis, rheumatoid arthritis, and many other autoimmune diseases.

Belimumab (Benlysta) is a monoclonal antibody developed by Human Genome Sciences and GlaxoSmithKline, with significant discovery input by Cambridge Antibody Technology, which specifically recognizes and inhibits the biological activity of B-Lymphocyte stimulator (BLyS) and is in clinical trials for treatment of Systemic lupus erythematosus and other auto-immune diseases.^[11]

Blisibimod, a fusion protein inhibitor of BAFF, is in development by Anthera Pharmaceuticals, also primarily for the treatment of systemic lupus erythematosus.^[12]

References[edit]

^ Shu HB, Hu WH, Johnson H (May 1999). "TALL-1 is a novel member of the TNF family that is down-regulated by mitogens". J. Leukoc. Biol. 65 (5): 680–3. PMID 10331498.
^ Schneider P, MacKay F, Steiner V, Hofmann K, Bodmer JL, Holler N, Ambrose C, Lawton P, Bixler S, Acha-Orbea H, Valmori D, Romero P, Werner-Favre C, Zubler RH, Browning JL, Tschopp J (June 1999). "BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth". J. Exp. Med. 189 (11): 1747–56. doi:10.1084/jem.189.11.1747. PMC 2193079. PMID 10359578.
^ "Entrez Gene: tumor necrosis factor (ligand) superfamily".
^ Oren DA, Li Y, Volovik Y, Morris TS, Dharia C, Das K, Galperina O, Gentz R, Arnold E (April 2002). "Structural basis of BLyS receptor recognition". Nat. Struct. Biol. 9 (4): 288–92. doi:10.1038/nsb769. PMID 11862220.
^ Daridon C, Youinou P, Pers JO (February 2008). "BAFF, APRIL, TWE-PRIL: who's who?". Autoimmun Rev 7 (4): 267–71. doi:10.1016/j.autrev.2007.05.002. PMID 18295728.
^ Wu Y, Bressette D, Carrell JA, Kaufman T, Feng P, Taylor K, Gan Y, Cho YH, Garcia AD, Gollatz E, Dimke D, LaFleur D, Migone TS, Nardelli B, Wei P, Ruben SM, Ullrich SJ, Olsen HS, Kanakaraj P, Moore PA, Baker KP (November 2000). "Tumor necrosis factor (TNF) receptor superfamily member TACI is a high affinity receptor for TNF family members APRIL and BLyS". J. Biol. Chem. 275 (45): 35478–85. doi:10.1074/jbc.M005224200. PMID 10956646.
^ Xia XZ, Treanor J, Senaldi G, Khare SD, Boone T, Kelley M, Theill LE, Colombero A, Solovyev I, Lee F, McCabe S, Elliott R, Miner K, Hawkins N, Guo J, Stolina M, Yu G, Wang J, Delaney J, Meng SY, Boyle WJ, Hsu H (July 2000). "TACI is a TRAF-interacting receptor for TALL-1, a tumor necrosis factor family member involved in B cell regulation". J. Exp. Med. 192 (1): 137–43. doi:10.1084/jem.192.1.137. PMC 1887716. PMID 10880535.
^ Roschke V, Sosnovtseva S, Ward CD, Hong JS, Smith R, Albert V, Stohl W, Baker KP, Ullrich S, Nardelli B, Hilbert DM, Migone TS (October 2002). "BLyS and APRIL form biologically active heterotrimers that are expressed in patients with systemic immune-based rheumatic diseases". J. Immunol. 169 (8): 4314–21. PMID 12370363.
^ Liu Y, Hong X, Kappler J, Jiang L, Zhang R, Xu L, Pan CH, Martin WE, Murphy RC, Shu HB, Dai S, Zhang G (May 2003). "Ligand-receptor binding revealed by the TNF family member TALL-1". Nature 423 (6935): 49–56. doi:10.1038/nature01543. PMID 12721620.
^ Shu HB, Johnson H (August 2000). "B cell maturation protein is a receptor for the tumor necrosis factor family member TALL-1". Proc. Natl. Acad. Sci. U.S.A. 97 (16): 9156–61. doi:10.1073/pnas.160213497. PMC 16838. PMID 10908663.
^ Navarra SV, Guzmán RM, Gallacher AE, Hall S, Levy RA, Jimenez RE, Li EK, Thomas M, Kim HY, León MG, Tanasescu C, Nasonov E, Lan JL, Pineda L, Zhong ZJ, Freimuth W, Petri MA; for the BLISS-52 Study Group. (February 2011). "Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial.". Lancet. 377 (9767): 721–431. doi:10.1016/S0140-6736(10)61354-2. PMID 21296403.
^ ClinicalTrials.gov. "PEARL-SC Trial: A Study of the Efficacy, Safety, and Tolerability of A 623 Administration in Subjects With Systemic Lupus Erythematosus.". United States National Institute of Health. Retrieved 2011-07-15.

External links[edit]

B-Cell Activating Factor at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. 体液性免疫応答 the humoral immune response
2. 分類不能型低ガンマグロブリン血症の病因 pathogenesis of common variable immunodeficiency
3. びまん性大細胞型B細胞性リンパ腫および原発性縦隔大細胞型B細胞リンパ腫の病理学 pathobiology of diffuse large b cell lymphoma and primary mediastinal large b cell lymphoma
4. 非ホジキンリンパ腫の病理の概要 overview of the pathobiology of the non hodgkin lymphomas
5. 肥満細胞由来のメディエーター mast cell derived mediators

English Journal

Anti-arthritic activity of N'-[(2,4-dihydroxyphenyl)methylidene]-2-(3,4-dimethyl-5,5-dioxidopyrazolo[4,3-c][1,2]benzothiazin-1(4H)-yl)acetohydrazide.

Shabbir A1, Shahzad M2, Ali A3, Zia-Ur-Rehman M4.
European journal of pharmacology.Eur J Pharmacol.2014 Sep 5;738:263-72. doi: 10.1016/j.ejphar.2014.05.045. Epub 2014 Jun 2.
Benzothiazine and pyrazole derivatives possess anti-inflammatory properties. Previously, synergism of both heterocyclic moieties into a single nucleus has shown to produce biologically active N'-arylmethylidene-2-(3,4-dimethyl-5,5-dioxidopyrazolo(4,3-c)(1,2)benzothiazin-2(4H)yl)acetohydrazides) comp
PMID 24943733

Fatty acid oxidation is dispensable for human macrophage IL-4-induced polarization.

Namgaladze D1, Brüne B2.
Biochimica et biophysica acta.Biochim Biophys Acta.2014 Sep;1841(9):1329-35. doi: 10.1016/j.bbalip.2014.06.007. Epub 2014 Jun 21.
Macrophage polarization elicits various metabolic alterations which in turn influence the polarized phenotype. Activation of glycolytic metabolism accompanies and supports macrophage pro-inflammatory M1 polarization. In contrast, M2 polarization of murine macrophages in response to the Th2 cytokine
PMID 24960101

Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity.

Schafer PH1, Parton A2, Capone L2, Cedzik D2, Brady H2, Evans JF3, Man HW4, Muller GW5, Stirling DI6, Chopra R2.
Cellular signalling.Cell Signal.2014 Sep;26(9):2016-29. doi: 10.1016/j.cellsig.2014.05.014. Epub 2014 May 29.
Apremilast, an oral small molecule inhibitor of phosphodiesterase 4 (PDE4), is in development for chronic inflammatory disorders, and has shown efficacy in psoriasis, psoriatic arthropathies, and Behçet's syndrome. In March 2014, the US Food and Drug Administration approved apremilast for the treat
PMID 24882690

Japanese Journal

内臓脂肪組織におけるB細胞活性化因子(BAFF)の役割 (特集肥満と消化器疾患)

阿部雅則,濱田麻穂,恩地森一
消化器内科 54(6), 645-649, 2012-06-00
NAID 40019386481

Serum BAFF and APRIL levels in patients with IgG4-related disease and their clinical significance.

Kiyama Kazuhiro,Kawabata Daisuke,Hosono Yuji,Kitagori Koji,Yukawa Naoichiro,Yoshifuji Hajime,Omura Koichiro,Fujii Takao,Mimori Tsuneyo
Arthritis research & therapy 14(2), 2012-04-24
… [Introduction]B cell-activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) play a crucial role in B cell development, survival, and antibody production. …
NAID 120004754361

Isolation and characterization of naïve follicular dendritic cells

Usui Kenta,Honda Shin-ichiro,Yoshizawa Yuichi,Nakahashi-Oda Chigusa,Tahara-Hanaoka Satoko,Shibuya Kazuko,Shibuya Akira,本多伸一郎,小田ちぐさ,田原聡子,渋谷和子,渋谷彰
Molecular immunology 50(3), 172-176, 2012-03-00
… Follicular dendritic cells (FDC) are specialized antigen-presenting cells to cognate B cells in the follicle of the lymphoid tissues. … FDC also support survival and proliferation of the B cells, leading to the germinal center formation. … The isolated FDC, which accounted for ∼0.2% of the spleen cells of naïve mice, were CD45－, FDC-M2+, and ICAM-1+, and supported the survival and LPS-induced proliferation of B cells. …
NAID 120004025777

「B細胞活性化因子」

Tumor necrosis factor (ligand) superfamily, member 13b
	; PDB rendering based on 1jh5.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1JH5, 1KD7, 1KXG, 1OQD, 1OQE, 1OSG, 1OTZ, 3V56
Identifiers
Symbols	TNFSF13B; BAFF; BLYS; CD257; DTL; TALL-1; TALL1; THANK; TNFSF20; ZTNF4
External IDs	OMIM: 603969 MGI: 1344376 HomoloGene: 48443 GeneCards: TNFSF13B Gene
Gene Ontology
Molecular function	• receptor binding; • cytokine activity; • tumor necrosis factor receptor binding; • protein binding;
Cellular component	• extracellular space; • plasma membrane; • integral to membrane;
Biological process	• B cell homeostasis; • positive regulation of germinal center formation; • immune response; • signal transduction; • cell proliferation; • positive regulation of cell proliferation; • positive regulation of B cell proliferation; • T cell costimulation; • B cell costimulation; • positive regulation of T cell proliferation; • immunoglobulin secretion;
	Sources: Amigo / QuickGO
Orthologs
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