Analysis of the oligomeric requirement for signaling by CD40 using soluble multimeric forms of its ligand, CD154
Analysis of the oligomeric requirement for signaling by CD40 using soluble multimeric forms of its ligand, CD154
We describe the construction of a novel soluble dodecameric form of CD154 (CD40 ligand) that is more effective than trimeric tCD154 in triggering B cell activation. Dodecameric surfactant protein (SP)-D-CD154 was more potent than tCD154 in inducing B cell proliferation over a wide range of concentrations. At saturating concentrations, the level of proliferation triggered by SP-D-CD154 was fourfold higher than that achieved with tCD154. Moreover, stimulation with dodecameric CD154 induced higher levels of the costimulatory molecules ICAM-1 and CD86. The higher activity of dodecameric CD154 when compared to trimeric CD154 is unlikely to be due to differences in their avidity for CD40, since both forms bound to CD40 strongly. Therefore, the extent of receptor clustering directlyregulates signaling by CD40.
TNF, TNF receptor superfamily, surfactant protein-D, B cell, receptor clustering
3094-3100
Haswell, Linsey E.
7e2a20d5-8dda-42dd-a956-962ce5446337
Glennie, Martin J.
9f6f0eff-4560-48c2-80cd-0ec116110ded
Al-Shamkhani, Aymen
0a40b3ce-9d71-4d41-9369-7212f0a84504
2001
Haswell, Linsey E.
7e2a20d5-8dda-42dd-a956-962ce5446337
Glennie, Martin J.
9f6f0eff-4560-48c2-80cd-0ec116110ded
Al-Shamkhani, Aymen
0a40b3ce-9d71-4d41-9369-7212f0a84504
Abstract
We describe the construction of a novel soluble dodecameric form of CD154 (CD40 ligand) that is more effective than trimeric tCD154 in triggering B cell activation. Dodecameric surfactant protein (SP)-D-CD154 was more potent than tCD154 in inducing B cell proliferation over a wide range of concentrations. At saturating concentrations, the level of proliferation triggered by SP-D-CD154 was fourfold higher than that achieved with tCD154. Moreover, stimulation with dodecameric CD154 induced higher levels of the costimulatory molecules ICAM-1 and CD86. The higher activity of dodecameric CD154 when compared to trimeric CD154 is unlikely to be due to differences in their avidity for CD40, since both forms bound to CD40 strongly. Therefore, the extent of receptor clustering directlyregulates signaling by CD40.
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Published date: 2001
Keywords:
TNF, TNF receptor superfamily, surfactant protein-D, B cell, receptor clustering
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Local EPrints ID: 26378
URI: http://eprints.soton.ac.uk/id/eprint/26378
ISSN: 0014-2980
PURE UUID: 49a0da52-1bf3-40c5-a776-74202d6372bf
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Date deposited: 24 Apr 2006
Last modified: 16 Mar 2024 03:02
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Author:
Linsey E. Haswell
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