LMP1 signaling can replace CD40 signaling in B cells in vivo and has unique features of inducing class-switch recombination to IgG1.

2.50
Hdl Handle:
http://hdl.handle.net/10033/23432
Title:
LMP1 signaling can replace CD40 signaling in B cells in vivo and has unique features of inducing class-switch recombination to IgG1.
Authors:
Rastelli, Julia; Hömig-Hölzel, Cornelia; Seagal, Jane; Müller, Werner; Hermann, Andrea C; Rajewsky, Klaus; Zimber-Strobl, Ursula
Abstract:
The Epstein-Barr virus (EBV) protein LMP1 is considered to be a functional homologue of the CD40 receptor. However, in contrast to the latter, LMP1 is a constitutively active signaling molecule. To compare B cell-specific LMP1 and CD40 signaling in an unambiguous manner, we generated transgenic mice conditionally expressing a CD40/LMP1 fusion protein, which retained the LMP1 cytoplasmic tail but has lost the constitutive activity of LMP1 and needs to be activated by the CD40 ligand. We show that LMP1 signaling can completely substitute CD40 signaling in B cells, leading to normal B-cell development, activation, and immune responses including class-switch recombination, germinal center formation, and somatic hypermutation. In addition, the LMP1-signaling domain has a unique property in that it can induce class-switch recombination to IgG1 independent of cytokines. Thus, our data indicate that LMP1 has evolved to imitate T-helper cell function allowing activation, proliferation, and differentiation of EBV-infected B cells independent of T cells.
Affiliation:
Institute of Clinical Molecular Biology and Tumor Genetics, GSF-National Research Center for Environment and Health, Munich, Germany.
Citation:
LMP1 signaling can replace CD40 signaling in B cells in vivo and has unique features of inducing class-switch recombination to IgG1. 2008, 111 (3):1448-55 Blood
Journal:
Blood
Issue Date:
1-Feb-2008
URI:
http://hdl.handle.net/10033/23432
DOI:
10.1182/blood-2007-10-117655
PubMed ID:
18006702
Type:
Article
Language:
en
ISSN:
0006-4971
Appears in Collections:
Publications of Dept. Experimental Immunology (EI)

Full metadata record

DC FieldValue Language
dc.contributor.authorRastelli, Julia-
dc.contributor.authorHömig-Hölzel, Cornelia-
dc.contributor.authorSeagal, Jane-
dc.contributor.authorMüller, Werner-
dc.contributor.authorHermann, Andrea C-
dc.contributor.authorRajewsky, Klaus-
dc.contributor.authorZimber-Strobl, Ursula-
dc.date.accessioned2008-04-15T12:32:49Z-
dc.date.available2008-04-15T12:32:49Z-
dc.date.issued2008-02-01-
dc.identifier.citationLMP1 signaling can replace CD40 signaling in B cells in vivo and has unique features of inducing class-switch recombination to IgG1. 2008, 111 (3):1448-55 Blooden
dc.identifier.issn0006-4971-
dc.identifier.pmid18006702-
dc.identifier.doi10.1182/blood-2007-10-117655-
dc.identifier.urihttp://hdl.handle.net/10033/23432-
dc.description.abstractThe Epstein-Barr virus (EBV) protein LMP1 is considered to be a functional homologue of the CD40 receptor. However, in contrast to the latter, LMP1 is a constitutively active signaling molecule. To compare B cell-specific LMP1 and CD40 signaling in an unambiguous manner, we generated transgenic mice conditionally expressing a CD40/LMP1 fusion protein, which retained the LMP1 cytoplasmic tail but has lost the constitutive activity of LMP1 and needs to be activated by the CD40 ligand. We show that LMP1 signaling can completely substitute CD40 signaling in B cells, leading to normal B-cell development, activation, and immune responses including class-switch recombination, germinal center formation, and somatic hypermutation. In addition, the LMP1-signaling domain has a unique property in that it can induce class-switch recombination to IgG1 independent of cytokines. Thus, our data indicate that LMP1 has evolved to imitate T-helper cell function allowing activation, proliferation, and differentiation of EBV-infected B cells independent of T cells.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshAntibodiesen
dc.subject.meshAntigens, CD40en
dc.subject.meshB-Lymphocytesen
dc.subject.meshCells, Cultureden
dc.subject.meshEnzyme Activationen
dc.subject.meshGerminal Centeren
dc.subject.meshImmunoglobulin Class Switchingen
dc.subject.meshImmunoglobulin Gen
dc.subject.meshMiceen
dc.subject.meshMice, Transgenicen
dc.subject.meshMitogen-Activated Protein Kinasesen
dc.subject.meshMutationen
dc.subject.meshNF-kappa Ben
dc.subject.meshSignal Transductionen
dc.subject.meshTransgenesen
dc.subject.meshViral Matrix Proteinsen
dc.titleLMP1 signaling can replace CD40 signaling in B cells in vivo and has unique features of inducing class-switch recombination to IgG1.en
dc.typeArticleen
dc.contributor.departmentInstitute of Clinical Molecular Biology and Tumor Genetics, GSF-National Research Center for Environment and Health, Munich, Germany.en
dc.identifier.journalBlooden

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