LMP1 signaling can replace CD40 signaling in B cells in vivo and has unique features of inducing class-switch recombination to IgG1.
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Authors
Rastelli, JuliaHömig-Hölzel, Cornelia
Seagal, Jane
Müller, Werner
Hermann, Andrea C
Rajewsky, Klaus
Zimber-Strobl, Ursula
Issue Date
2008-02-01
Metadata
Show full item recordAbstract
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.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 BloodAffiliation
Institute of Clinical Molecular Biology and Tumor Genetics, GSF-National Research Center for Environment and Health, Munich, Germany.Journal
BloodPubMed ID
18006702Type
ArticleLanguage
enISSN
0006-4971ae974a485f413a2113503eed53cd6c53
10.1182/blood-2007-10-117655
Scopus Count
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