Isolation of cDNAS encoding T-BAM, a surface glycoprotein on CD4+ T cells mediating contact-dependent helper function for B cells: Identity with the CD40-ligand

Covey, Lori R.; Cleary, Aileen M.; Yellin, Michael; Ware, Randle; Sullivan, G J; Belko, John; Parker, Mary A.; Rothman, Paul B.; Chess, Leonard; Lederman, Seth

doi:10.1016/0161-5890(94)90066-3

Cited by 25 publications

(15 citation statements)

References 35 publications

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“…N-terminal sequence data for 33-kDa CD40L matches the predicted translated protein sequence of CD40L (4,24), indicating that Met-1 is preserved in the matured protein. The p31 protein sequence starts with Met-21 indicating that the difference between full-length CD40L and p31 is the result of N-terminal truncation (4,24). The p18 protein starts with Gln-114 of the CD40L sequence and therefore is missing the entire cytoplasmic domain, the transmembrane region, and the extracellular stalk of the CD40L.…”

Section: Immunoprecipitation Of the Metabolically Labeled Cd40l-mentioning

confidence: 89%

“…Control human IgG 1 antibody was purchased from Protos Immunoresearch (San Francisco, CA). Rb784 antiserum was generated by immunizing the rabbit with a synthetic peptide corresponding to the N-terminal 15 amino acids (MIETYNQTSPRSAAT) of CD40L (4,24) coupled to keyhole limpet hemocyanin (KLH) using the maleimideactivated KLH kit (Pierce) following the manufacturer's protocol. COS7 cells were maintained in Dulbecco's modified Eagle's medium with 10% heat inactivated FBS.…”

Section: Methodsmentioning

confidence: 99%

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Heteromultimeric Complexes of CD40 Ligand Are Present on the Cell Surface of Human T Lymphocytes

Hsu

Lucci

et al. 1997

Journal of Biological Chemistry

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CD40 ligand (CD40L), a 33-kDa type II membrane glycoprotein expressed primarily on activated CD4؉ T lymphocytes, is responsible for the helper function of T cells on resting B cells in a non-antigen-dependent, non-major histocompatability complex-restricted fashion. Interaction of CD40L with its receptor CD40 induces proliferation of and isotype switching in B lymphocytes. Recently we solved the x-ray structure of recombinant soluble CD40L and showed that, similar to other members of the tumor necrosis factor family, CD40L indeed exists as a trimer. We now report that, under normal physiological conditions, CD40L molecules exist as heteromultimeric complexes. These CD40L complexes, made of the full length and smaller fragments of CD40L, are present on the cell surface of T lymphocytes and are capable of interacting with CD40 molecule. A prominent fragment with a mass of 31 kDa accounts for as much as half of the CD40L on the surface of Jurkat cells. Nterminal sequence data revealed that this fragment lacks the cytoplasmic tail. A minor 18-kDa fragment of CD40L was also characterized which lacks the cytoplasmic tail, transmembrane region, and stalk region of the extracellular domain. The presence of CD40L heteromultimeric variants implies an additional regulation of the functional activity of this ligand complex.

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Section: Immunoprecipitation Of the Metabolically Labeled Cd40l-mentioning

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Heteromultimeric Complexes of CD40 Ligand Are Present on the Cell Surface of Human T Lymphocytes

Hsu

Lucci

et al. 1997

Journal of Biological Chemistry

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“…These mechanisms probably serve to focus productive cognate contact-dependent CD40L+, CD4+ T cell interactions with appropriate target cells. However, CD40L expression may not be limited to CD4+ T cells since studies indicate that CD8+ T cells (41,44), mast cells (49, eosinophils (46), and B cells (47) also can express CD40L. Moreover, there is increased CD40L expression on peripheral blood CD4+ T cells, CD8+ T cells, and B cells in active SLE (48).…”

Section: Discussionmentioning

confidence: 99%

Immunohistologic analysis of renal CD40 and CD40L expression in lupus nephritis and other glomerulonephritides

Yellin

D’Agati

Parkinson

et al. 1997

Arthritis & Rheumatism

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148

115

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Objective. To investigate potential mechanisms by which CD40L-mediated signals may be involved in the pathogenesis of lupus glomerulonephritis (GN).Methods. Renal in situ CD40L and CD40 expression was examined in patient biopsy specimens. Immunohistochemical studies were performed on frozen sections utilizing anti-CD40L monoclonal antibody (MAb), anti-CD40 MAb, or control MAb. As controls, we analyzed normal kidney specimens and specimens obtained from patients with IgA nephropathy, focal segmental glomerulosclerosis, minimal change disease, idiopathic membranous GN, and antineutrophil cytoplasmic antibodypositive pauci-immune GN. Staining distribution was noted and staining intensity scored on a semiquantitative scale of 0 (no staining) to 3+ (intense staining).Results. In normal kidney, CD40 was expressed on parietal epithelial cells, mesangial cells, endothelial cells, and distal tubules but not proximal tubules. Glomerular and tubular CD40 expression was markedly up-regulated in class I11 and class IV lupus GN, where there was intense staining of crescents, proximal and distal tubules, and interstitial mononuclear cells. In contrast, CD40 expression in class V lupus GN was similar to that in normal kidney. Interstitial mononuclear cells expressing CD40L were present in class IV lupus GN. However, these findings were not unique to lupus GN: up-regulation of CD40 and CD40L expres- Submitted for publication June 3, 1996; accepted in revised form July 17, 1996. sion was similarly observed in other inflammatory renal diseases.Conclusion. This study shows that CD40 is expressed on a variety of renal parenchymal and nonparenchymal cells in normal kidney. Renal CD40 expression is up-regulated in class I11 and class IV lupus nephritis, as well as in other inflammatory renal diseases, and is associated with the presence of CD40L+ mononuclear cells.

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“…293 cells are derived from adenovirus 5-transformed primary human embryonal kidney cells (American Type Culture Collection). The 293/CD40L line was constructed by the stable transfection of pCT-BAM into 293 cells as described previously (35). 293 cells were cultured in DMEM/F12 supplemented with 10% FCS, 50 U/ml penicillin, 50 g/ml streptomycin, and 1 mM L-glutamine at 37°C and 5% CO 2.…”

Section: Cell Culturementioning

confidence: 99%

A Novel NF-κB-Regulated Site within the Human Iγ1 Promoter Requires p300 for Optimal Transcriptional Activity

Dryer

Covey

2005

The Journal of Immunology

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Transcriptional activation of germline (GL) promoters occurs through binding of NF-κB to three evolutionarily conserved sites within a CD40 response region in the human and mouse GL Iγ and Iε promoters. Here we identify and characterize a novel NF-κB binding site (κB6) within the human GL Iγ1 promoter that plays an essential role in basal- and CD40-induced transcription. This site is adjacent to identified CREB/activating transcription factor (ATF) sites, present in the Iγ1 but not the Iγ3 promoter, which are important for the amplification of transcription. Our data suggest a cohesive protein complex regulating Iγ1 promoter activity because disruption of any individual NF-κB or CREB/ATF site markedly lowers the overall inducible activity of the promoter. In addition, alteration of helical phasing within the promoter indicates spatial orientation of CREB/ATF and NF-κB, proteins contributes directly to promoter activity. We found that CREB and p50 transactivators, as well as coactivator p300, interact in vivo with the Iγ1 promoter in the presence and absence of CD40 signaling in Ramos and primary B cells. However, the level of CREB and p300 binding differs as a consequence of activation in primary B cells. Furthermore, overexpression of p300, and not a mutant lacking acetyltransferase activity, significantly increases Iγ1 construct-specific transcription. Together these data support a model whereby CREB and multiple NF-κB complexes bind to the Iγ1 promoter and recruit p300. CD40 signals induce p300-dependent changes that result in optimal Iγ1 promoter activity.

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Isolation of cDNAS encoding T-BAM, a surface glycoprotein on CD4+ T cells mediating contact-dependent helper function for B cells: Identity with the CD40-ligand

Cited by 25 publications

References 35 publications

Heteromultimeric Complexes of CD40 Ligand Are Present on the Cell Surface of Human T Lymphocytes

Heteromultimeric Complexes of CD40 Ligand Are Present on the Cell Surface of Human T Lymphocytes

Immunohistologic analysis of renal CD40 and CD40L expression in lupus nephritis and other glomerulonephritides

A Novel NF-κB-Regulated Site within the Human Iγ1 Promoter Requires p300 for Optimal Transcriptional Activity

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