発現細胞

B細胞
マクロファージ
樹状細胞
basal epithelial cells

機能

CD40Lと結合

B細胞

receptor for costimulatory signal for B cells (IMM.785)
B細胞の増殖、分化、isotype switching of B cells (IMM.785)

PrepTutorEJDIC

certificate of deposit / (また『C.D.』)Civil Defense民間防衛

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/05/28 19:14:47」(JST)

wiki en

[Wiki en表示]

CD40 is a costimulatory protein found on antigen presenting cells and is required for their activation. The binding of CD154 (CD40L) on T_H cells to CD40 activates antigen presenting cells and induces a variety of downstream effects.

Deficiency can cause Hyper-IgM syndrome type 3.

Function

The protein receptor encoded by this gene is a member of the TNF-receptor superfamily. This receptor has been found to be essential in mediating a broad variety of immune and inflammatory responses including T cell-dependent immunoglobulin class switching, memory B cell development, and germinal center formation. AT-hook transcription factor AKNA is reported to coordinately regulate the expression of this receptor and its ligand, which may be important for homotypic cell interactions. The TNFR-receptor associated factor adaptor proteins TRAF1, TRAF2, TRAF6 and possibly TRAF5 interact with this receptor and serve as mediators of the signal transduction. The interaction of this receptor and its ligand is found to be necessary for amyloid-beta-induced microglial activation, and thus is thought to be an early event in Alzheimer disease pathogenesis. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported.^[1]

Specific effects on cells

In the macrophage, the primary signal for activation is IFN-γ from Th1 type CD4 T cells. The secondary signal is CD40L (CD154) on the T cell which binds CD40 on the macrophage cell surface. As a result, the macrophage expresses more CD40 and TNF receptors on its surface which helps increase the level of activation. The increase in activation results in the induction of potent microbicidal substances in the macrophage, including reactive oxygen species and nitric oxide, leading to the destruction of ingested microbe.

The B cell can present antigens to helper T cells. If an activated T cell recognizes the peptide presented by the B cell, the CD40L on the T cell binds to the B cell's CD40 receptor, causing resting B cell activation. The T cell also produces IL-4, which directly influences B cells. As a result of this net stimulation, the B cell can undergo division, antibody isotype switching, and differentiation to plasma cells. The end-result is a B cell that is able to mass-produce specific antibodies against an antigenic target. Early evidence for these effects were that in CD40 or CD154 deficient mice, there is little class switchingor germinal centre formation, and immune responses are severely inhibited.

The expression of CD40 is diverse. CD40 is constitutively expressed by antigen presenting cells, including dendritic cells, B cells and macrophages. It can also be expressed by endothelial cells, smooth muscle cells, fibroblasts and epithelial cells. Consistent with its widespread expression on normal cells, CD40 is also expressed on a wide range of tumor cells, including non-Hodgkin's and Hodgkin's lymphomas, myeloma and some carcinomas including nasopharynx, bladder, cervix, kidney and ovary. CD40 is also expressed on B cell precursors in the bone marrow, and there is some evidence that CD40-CD154 interactions may play a role in the control of B cell haematopoiesis (10)

Interactions

CD40 (protein) has been shown to interact with TRAF2,^[2]^[3]^[4] TRAF3,^[3]^[5]^[6]^[7] TRAF6,^[3]^[7] TRAF5^[3]^[8] and TTRAP.^[9]

References

^ "Entrez Gene: CD40 CD40 molecule, TNF receptor superfamily member 5". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=958.
^ McWhirter, S M; Pullen S S, Holton J M, Crute J J, Kehry M R, Alber T (July 1999). "Crystallographic analysis of CD40 recognition and signaling by human TRAF2". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 96 (15): 8408–13. doi:10.1073/pnas.96.15.8408. ISSN 0027-8424. PMC 17529. PMID 10411888. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=17529.
^ ^a ^b ^c ^d Tsukamoto, N; Kobayashi N, Azuma S, Yamamoto T, Inoue J (February 1999). "Two differently regulated nuclear factor κB activation pathways triggered by the cytoplasmic tail of CD40". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 96 (4): 1234–9. doi:10.1073/pnas.96.4.1234. ISSN 0027-8424. PMC 15446. PMID 9990007. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=15446.
^ Malinin, N L; Boldin M P, Kovalenko A V, Wallach D (February 1997). "MAP3K-related kinase involved in NF-kappaB induction by TNF, CD95 and IL-1". Nature (ENGLAND) 385 (6616): 540–4. doi:10.1038/385540a0. ISSN 0028-0836. PMID 9020361.
^ Hu, H M; O'Rourke K, Boguski M S, Dixit V M (December 1994). "A novel RING finger protein interacts with the cytoplasmic domain of CD40". J. Biol. Chem. (UNITED STATES) 269 (48): 30069–72. ISSN 0021-9258. PMID 7527023.
^ Ni, C Z; Welsh K, Leo E, Chiou C K, Wu H, Reed J C, Ely K R (September 2000). "Molecular basis for CD40 signaling mediated by TRAF3". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 97 (19): 10395–9. doi:10.1073/pnas.97.19.10395. ISSN 0027-8424. PMC 27035. PMID 10984535. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=27035.
^ ^a ^b Roy, N; Deveraux Q L, Takahashi R, Salvesen G S, Reed J C (December 1997). "The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases". EMBO J. (ENGLAND) 16 (23): 6914–25. doi:10.1093/emboj/16.23.6914. ISSN 0261-4189. PMC 1170295. PMID 9384571. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1170295.
^ Ishida, T K; Tojo T, Aoki T, Kobayashi N, Ohishi T, Watanabe T, Yamamoto T, Inoue J (September 1996). "TRAF5, a novel tumor necrosis factor receptor-associated factor family protein, mediates CD40 signaling". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 93 (18): 9437–42. doi:10.1073/pnas.93.18.9437. ISSN 0027-8424. PMC 38446. PMID 8790348. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=38446.
^ Pype, S; Declercq W, Ibrahimi A, Michiels C, Van Rietschoten J G, Dewulf N, de Boer M, Vandenabeele P, Huylebroeck D, Remacle J E (June 2000). "TTRAP, a novel protein that associates with CD40, tumor necrosis factor (TNF) receptor-75 and TNF receptor-associated factors (TRAFs), and that inhibits nuclear factor-kappa B activation". J. Biol. Chem. (UNITED STATES) 275 (24): 18586–93. doi:10.1074/jbc.M000531200. ISSN 0021-9258. PMID 10764746.

Carlring, Jennifer; AlTaher HM, Clark S, Chen X, Latimer SL, Jenner T, Buckle AM, Heath AW (2011). "CD154-CD40 interactions in the control of B cell hematopoiesis". J.Leuk Biol 89 (5): 697–706. doi:10.1189/jlb.0310179.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 体液性免疫応答 the humoral immune response
2. 複合免疫不全 combined immunodeficiencies
3. BおよびTリンパ球の正常な発生 normal b and t lymphocyte development
4. 移植免疫 transplantation immunobiology
5. 関節リウマチのT細胞標的療法 t cell targeted therapies for rheumatoid arthritis

English Journal

TLR2- and 4-independent immunomodulatory effect of high molecular weight components from Ascaris suum.

Favoretto BC1, Silva SR2, Jacysyn JF3, Câmara NO4, Faquim-Mauro EL5.Author information 1Laboratory of Immunopathology, Butantan Institute, São Paulo, SP, Brazil.2Pasteur Institute, São Paulo, Brazil.3LIM62 Faculty of Medicine, University of São Paulo, São Paulo, Brazil.4Department of Immunology, University of São Paulo, São Paulo, Brazil.5Laboratory of Immunopathology, Butantan Institute, São Paulo, SP, Brazil. Electronic address: elianafaquim@butantan.gov.br.AbstractComponents of high molecular-weight (PI) obtained from Ascaris suum extract down-regulate the Th1/Th2-related immune responses induced by ovalbumin (OVA)-immunization in mice. Furthermore, the PI down-modulates the ability of dendritic cells (DCs) to activate T lymphocytes by an IL-10-mediated mechanism. Here, we evaluated the role of toll like receptors 2 and 4 (TLR2 and 4) in the modulatory effect of PI on OVA-specific immune response and the PI interference on DC full activation. An inhibition of OVA-specific cellular and humoral responses were observed in wild type (WT) or in deficient in TLR2 (TLR2(-/-)) or 4 (TLR4(-/-)) mice immunized with OVA plus PI when compared with OVA-immunized mice. Low expression of class II MHC, CD40, CD80 and CD86 molecules was observed in lymph node (LN) cells from WT, TLR2(-/-) or TLR4(-/-) mice immunized with OVA plus PI compared with OVA-primed cells. We also verified that PI was able to modulate the activation of DCs derived from bone marrow of WT, TLR2(-/-) or TLR4(-/-) mice induced in vitro by agonists of TLRs, as observed by a decreased expression of class II MHC and costimulatory molecules and by low secretion of pro-inflammatory cytokines. Its effect was accompanied by IL-10 synthesis. In this sense, the modulatory effect of PI on specific-immune response and DC activation is independent of TLR2 or TLR4.
Molecular immunology.Mol Immunol.2014 Mar;58(1):17-26. doi: 10.1016/j.molimm.2013.10.011. Epub 2013 Nov 19.
Components of high molecular-weight (PI) obtained from Ascaris suum extract down-regulate the Th1/Th2-related immune responses induced by ovalbumin (OVA)-immunization in mice. Furthermore, the PI down-modulates the ability of dendritic cells (DCs) to activate T lymphocytes by an IL-10-mediated mecha
PMID 24263181

Increased expression of herpesvirus entry mediator in 1,25‑dihydroxyvitamin D3‑treated mouse bone marrow‑derived dendritic cells promotes the generation of CD4+CD25+Foxp3+ regulatory T cells.

Huang Y1, Zhao Y2, Ran X2, Wang C1.Author information 1Institute of Respiratory Diseases, Xinqiao Hospital, The Third Military Medical University, Chongqing 430037, P.R. China.2Department of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, Chongqing 404000, P.R. China.AbstractDendritic cells (DCs) can initiate immune responses or induce immune tolerance. 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] is a secosteroid hormone that can induce tolerogenic dendritic cells favoring the induction of regulatory T cells (Treg). The present study revealed a tolerogenic effect of 1,25(OH)2D3 on the phenotype and function of ovalbumin (OVA)‑activated mouse bone marrow‑derived DCs. Three inhibitory molecules associated with tolerogenic DCs, programmed death‑ligand-1 (PD‑L1), PD‑L2 and herpesvirus entry mediator (HVEM) and the expression of co‑stimulatory molecules (CD80, CD86 and CD40) on 1,25(OH)2D3‑treated DCs were examined. The levels of interleukin (IL)‑2, IL‑6 and IL‑10 secreted by 1,25(OH)2D3‑treated DCs were analyzed. The capability of 1,25(OH)2D3‑treated DCs to induce CD4+CD25+Foxp3+ Treg and the stimulation of allogeneic CD4+ T‑cell proliferation in mixed lymphocyte reaction (MLR) was studied. 1,25(OH)2D3‑treated DCs induced up to 21.0‑fold upregulation of the HVEM expression and 4.1‑fold enhancement of the HVEM expression upon activation with OVA [OVA‑D3/immature (im)DCs]. PD‑L1 was not affected by 1,25(OH)2D3‑treated DCs and downregulated PD‑L2 expression on 1,25(OH)2D3‑treated DCs and OVA‑D3/imDC. The expression of co‑stimulatory molecules (CD80, CD86 and CD40) was downregulated in 1,25(OH)2D3‑treated DCs and OVA‑D3/imDC. Furthermore, 1,25(OH)2D3‑treated DCs secreted much higher levels of IL‑10, however lower levels of IL‑2 and IL‑6 compared with the activated control DCs. Together with this pattern of cytokines, 1,25(OH)2D3‑treated DCs exhibited low allogeneic CD4+ T‑cell stimulatory activity and a higher number of CD4+CD25+Foxp3+ cells in the MLR cultures but not in the activated control DCs. These findings indicate that 1,25(OH)2D3 possesses the immunosuppressive properties by upregulating the expression of the inhibitory molecules, HVEM, which may be therapeutically useful in controlling chronic immune and/or inflammatory diseases.
Molecular medicine reports.Mol Med Rep.2014 Mar;9(3):813-8. doi: 10.3892/mmr.2013.1874. Epub 2013 Dec 18.
Dendritic cells (DCs) can initiate immune responses or induce immune tolerance. 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] is a secosteroid hormone that can induce tolerogenic dendritic cells favoring the induction of regulatory T cells (Treg). The present study revealed a tolerogenic effect of 1,25(
PMID 24366217

Glucocorticoid inhibition of activation-induced cytidine deaminase expression in human B lymphocytes.

Benko AL1, Olsen NJ2, Kovacs WJ3.Author information 1Division of Endocrinology, Diabetes, and Metabolism, The Pennsylvania State University, College of Medicine, Milton S. Hershey Medical Center, Hershey, PA 17033, United States.2Division of Rheumatology, The Pennsylvania State University, College of Medicine, Milton S. Hershey Medical Center, Hershey, PA 17033, United States.3Division of Endocrinology, Diabetes, and Metabolism, The Pennsylvania State University, College of Medicine, Milton S. Hershey Medical Center, Hershey, PA 17033, United States. Electronic address: wkovacs@hmc.psu.edu.AbstractWe examined whether glucocorticoids could modulate the expression of activation-induced cytidine deaminase (AICDA), the principal regulator of the processes of immunoglobulin gene somatic hypermutation and class switch recombination in B lymphocytes. Treatment of human B cells with IL-4 and anti-CD40 antibody for 18-20h resulted in induction of expression of AICDA mRNA by over 10-fold. Dexamethasone at 10nM concentration inhibited AICDA induction by an average of 51.8% (p<0.0001). These effects of glucocorticoids were found to be dose dependent in the physiologic range and were reversible by co-treatment with a glucocorticoid receptor antagonist. Human B cell viability and proliferation were unaltered by glucocorticoid treatment. These data demonstrate that physiologic concentrations of glucocorticoids can act on human B lymphocytes through glucocorticoid receptor-mediated mechanisms to diminish the expression of AICDA, a key regulator of humoral immune responses.
Molecular and cellular endocrinology.Mol Cell Endocrinol.2014 Feb 15;382(2):881-7. doi: 10.1016/j.mce.2013.11.001. Epub 2013 Nov 15.
We examined whether glucocorticoids could modulate the expression of activation-induced cytidine deaminase (AICDA), the principal regulator of the processes of immunoglobulin gene somatic hypermutation and class switch recombination in B lymphocytes. Treatment of human B cells with IL-4 and anti-CD4
PMID 24239615

Japanese Journal

シンポジウム「統合医科学研究所(TIIMS)の紹介と今後の展望」(2)関節リウマチの遺伝子解析

谷口敦夫
東京女子医科大学雑誌 81(3), 198-203, 2011-06-25
… MHC領域、T細胞活性化やCD40シグナル伝達に関与する分子の遺伝子多型などが遺伝的リスク要因として報告されている。 …
NAID 110008585264

Allogenic mixed chimerism prevented autoimmune thrombocytopenia in BXSB lupus mice receiving donor BMT with nonlymphoablative conditioning of low-dose TBI and anti-CD40L mAb

Takeuchi Emiko
The Kitasato medical journal 41(1), 50-56, 2011-03
NAID 40018724980

Related Pictures

★リンクテーブル★

リンク元	「表面抗原分類」「高IgM症候群」「サイトカイン受容体」「CD154」
拡張検索	「CD40抗原」「CD40タンパク質」「CD40リガンド」「CD40L」
関連記事	「CD」「CD4」

「表面抗原分類」

CD40 molecule, TNF receptor superfamily member 5
	; Rendering based on PDB 1CDF.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1CZZ, 1D00, 1FLL, 1LB6, 3QD6
Identifiers
Symbols	CD40; Bp50; CDW40; TNFRSF5; p50
External IDs	OMIM: 109535 MGI: 88336 HomoloGene: 954 ChEMBL: 1250358 GeneCards: CD40 Gene
Gene Ontology
Molecular function	• signal transducer activity; • receptor activity; • protein binding; • enzyme binding;
Cellular component	• extracellular region; • plasma membrane; • plasma membrane; • integral to plasma membrane; • external side of plasma membrane; • CD40 receptor complex; • intracellular membrane-bounded organelle;
Biological process	• positive regulation of protein phosphorylation; • immune response-regulating cell surface receptor signaling pathway; • protein complex assembly; • cellular calcium ion homeostasis; • inflammatory response; • signal transduction; • platelet activation; • positive regulation of B cell proliferation; • positive regulation of interleukin-12 production; • positive regulation of Rac GTPase activity; • B cell proliferation; • positive regulation of tyrosine phosphorylation of Stat1 protein; • positive regulation of Cdc42 GTPase activity; • positive regulation of I-kappaB kinase/NF-kappaB cascade; • positive regulation of MAP kinase activity; • positive regulation of transcription from RNA polymerase II promoter; • positive regulation of isotype switching to IgG isotypes; • regulation of immune response; • regulation of immunoglobulin secretion; • positive regulation of NF-kappaB transcription factor activity; • defense response to virus; • cellular response to mechanical stimulus; • positive regulation of protein kinase C signaling cascade; • positive regulation of endothelial cell apoptosis;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	This box: view; talk; edit;

　　[★]

英: cluster of differentiation, CD

細胞の表面抗原を認識する抗体を整理した分類

Bリンパ球 CD10,CD19,CD20

Tリンパ球 CD2,CD3,CD5,CD7

幹細胞 CD34

顆粒球 CD13,CD33

単球 CD14：LPSをリガンドとし、Toll-like receptorと共役して細胞内シグナルを伝達する分子。

巨核球 CD41(GpIIb),CD42(GpIb)

NK細胞：CD16(IgGのFc部に対する受容体)、CD56(NCAM-I)

CD1	CD21	CD41	CD61	CD81
CD2	CD22	CD42	CD62	CD82
CD3	CD23	CD43	CD63	CD83
CD4	CD24	CD44	CD64	CD84
CD5	CD25	CD45	CD65	CD85
CD6	CD26	CD46	CD66	CD86
CD7	CD27	CD47	CD67	CD87
CD8	CD28	CD48	CD68	CD88
CD9	CD29	CD49	CD69	CD89
CD10	CD30	CD50	CD70	CD90
CD11	CD31	CD51	CD71	CD91
CD12	CD32	CD52	CD72	CD92
CD13	CD33	CD53	CD73	CD93
CD14	CD34	CD54	CD74	CD94
CD15	CD35	CD55	CD75	CD95
CD16	CD36	CD56	CD76	CD96
CD17	CD37	CD57	CD77	CD97
CD18	CD38	CD58	CD78	CD98
CD19	CD39	CD59	CD79	CD99
CD20	CD40	CD60	CD80	CD100