Epstein-Barr virus LMP2A alters in vivo and in vitro models of B-cell anergy, but not deletion, in response to autoantigen.

Abstract:

:A significant percentage of the population latently harbors Epstein-Barr virus (EBV) in B cells. One EBV-encoded protein, latent membrane protein 2A (LMP2A), is expressed in tissue culture models of EBV latent infection, in human infections, and in many of the EBV-associated proliferative disorders. LMP2A constitutively activates proteins involved in the B-cell receptor (BCR) signal transduction cascade and inhibits the antigen-induced activation of these proteins. In the present study, we investigated whether LMP2A alters B-cell receptor signaling in primary B cells in vivo and in vitro. LMP2A does not inhibit antigen-induced tolerance in response to strong stimuli in an in vivo tolerance model in which B cells are reactive to self-antigen. In contrast, LMP2A bypasses anergy induction in response to low levels of soluble hen egg lysozyme (HEL) both in vivo and in vitro as determined by the ability of LMP2A-expressing HEL-specific B cells to proliferate and induce NF-kappaB nuclear translocation after exposure to low levels of antigen. Furthermore, LMP2A induces NF-kappaB nuclear translocation independent of BCR cross-linking. Since NF-kappaB is required to bypass tolerance induction, this LMP2A-dependent NF-kappaB activation may complete the tolerogenic signal induced by low levels of soluble HEL. Overall, the findings suggest that LMP2A may not inhibit BCR-induced signals under all conditions as previously suggested by studies with EBV immortalized B cells.

journal_name

J Virol

journal_title

Journal of virology

authors

Swanson-Mungerson MA,Caldwell RG,Bultema R,Longnecker R

doi

10.1128/JVI.79.12.7355-7362.2005

subject

Has Abstract

pub_date

2005-06-01 00:00:00

pages

7355-62

issue

12

eissn

0022-538X

issn

1098-5514

pii

79/12/7355

journal_volume

79

pub_type

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