Epstein-Barr virus LMP2A-induced B-cell survival in two unique classes of EμLMP2A transgenic mice

Robert G. Caldwell, R. Clark Brown, Richard Longnecker*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

106 Scopus citations

Abstract

Latent membrane protein 2A (LMP2A) is one of only two viral proteins expressed during latent Epstein-Barr virus (EBV) infections in human peripheral B cells. LMP2A blocks B-cell receptor (BCR) signal transduction in vitro by modulation of the Syk and Lyn protein tyrosine kinases. Five genetically unique LMP2A transgenic mouse lines (EμLMP2A) with B-cell lineage expression of LMP2A were generated in this study to analyze the importance of LMP2A expression in vivo. These animals can be grouped into EμLMP2A(BCR+) (TgB, Tg6, and TgC) and EμLMP2A(BCR-) (Tg7 and TgE) lines based on B-cell phenotype. LMP2A expression in bone marrow cells of EμLMP2A(BCR-) lines was associated with a bypass of normal B-lymphocyte developmental checkpoints inasmuch as immunoglobulin light-chain gene rearrangement occurred in the absence of complete immunoglobulin heavy-chain gene rearrangement. The resulting BCR-negative B cells were able to exit the bone marrow and colonize peripheral lymphoid organs. LMP2A expression in EμLMP2A(BCR+) lines was not associated with altered B-cell development in a genetically wild-type background. When crossed into a recombinase activating null (RAG(-/-)) genetic background, LMP2A expression in either RAG(-/-) EμLMP2A(BCR+) or RAG(-/-) EμLMP2A(BCR-) animals was able to provide a survival signal to BCR-negative splenic B cells. Additionally, bone marrow cells from all EμLMP2A animals were able to proliferate in response to interleukin-7-dependent developmental signals in vitro. These studies illustrate that LMP2A can provide a survival signal to BCR-negative B cells in two different groups of EμLMP2A transgenic mice.

Original languageEnglish (US)
Pages (from-to)1101-1113
Number of pages13
JournalJournal of virology
Volume74
Issue number3
DOIs
StatePublished - 2000

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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