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Journal of Virology, February 2000, p. 1101-1113, Vol. 74, No. 3
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Epstein-Barr Virus LMP2A-Induced B-Cell Survival in Two Unique Classes of EµLMP2A Transgenic Mice

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

Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611

Received 20 August 1999/Accepted 26 October 1999

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 EµLMP2ABCR+ (TgB, Tg6, and TgC) and EµLMP2ABCR- (Tg7 and TgE) lines based on B-cell phenotype. LMP2A expression in bone marrow cells of EµLMP2ABCR- 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 EµLMP2ABCR+ 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-/- EµLMP2ABCR+ or RAG-/- EµLMP2ABCR- 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.

* Corresponding author. Mailing address: Department of Microbiology-Immunology, Northwestern University Medical School, 303 E. Chicago Ave., Chicago, IL 60611. Phone: (312) 503-0467. Fax: (312) 503-1339. E-mail: r-longnecker{at}nwu.edu.

Journal of Virology, February 2000, p. 1101-1113, Vol. 74, No. 3
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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