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TRAF Binding is Required for a Distinct Subset of in vivo B Cell Functions of the Oncoprotein LMP1
Journal article   Peer reviewed

TRAF Binding is Required for a Distinct Subset of in vivo B Cell Functions of the Oncoprotein LMP1

Kelly M Arcipowski and Gail A Bishop
The Journal of immunology (1950), Vol.189(11), pp.5165-5170
12/01/2012
DOI: 10.4049/jimmunol.1201821
PMCID: PMC3504128
PMID: 23109728

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Abstract

EBV-encoded latent membrane protein 1 (LMP1) is important for EBV contributions to B cell transformation and many EBV-associated malignancies, as well as EBV-mediated exacerbation of autoimmunity. LMP1 functionally mimics tumor necrosis factor receptor (TNFR) superfamily member CD40, but LMP1 signals and downstream effects are amplified and sustained compared to CD40. CD40 and LMP1 both utilize TNFR-associated factor (TRAF) adaptor proteins, but in distinct ways. LMP1 functions require TRAFs 3, 5, and 6, which interact with LMP1. However, TRAFs can also contribute to signaling in the absence of direct interactions with cell surface receptors, so we investigated whether their roles in LMP1 in vivo functions require direct association. We show here that the LMP1 TRAF binding site was required for LMP1-mediated autoantibody production, the germinal center response to immunization, and optimal production of several isotypes of Ig, but not LMP1-dependent enlargement of secondary lymphoid organs in transgenic (Tg) mice. Thus, LMP1 in vivo effects can be mediated via both TRAF binding-dependent and -independent pathways. Together with our previous findings, these results indicate that TRAF-dependent receptor functions may not always require TRAF-receptor binding. These data suggest that TRAF-mediated signaling pathways, such as those of LMP1, may be more diverse than previously appreciated. This finding has significant implications for receptor and TRAF-targeted therapies.

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