LMP2A Survival and Developmental Signals Are Transmitted through Btk-Dependent and Btk-Independent Pathways
Copyright policy )LMP2A Survival and Developmental Signals Are Transmitted through Btk-Dependent and Btk-Independent Pathways
The latent membrane protein 2A (LMP2A) of Epstein--Barr virus (EBV) has been implicated in controlling viral latency due to the ability of LMP2A to block B cell antigen receptor (BCR) signaling in vitro and to alter B cell development and enhance B cell survival in vivo. These LMP2A functions require interactions with the protein tyrosine kinases Syk and Lyn. However, a role for the Bruton's tyrosine kinase (Btk) has not been investigated for these LMP2A functions. To investigate whether Btk is important for LMP2A developmental and survival signals in vivo, LMP2A transgenic animals were mated to Btk deficient (Btk(-/-)) mice. Unlike LMP2A(+), Btk(+/+) transgenic littermate controls, LMP2A(+), Btk(-/-) animals do not generate immunoglobulin (Ig) receptorless B cells in the periphery and instead produce Ig(+) B cells similar to those in the Btk(-/-) mice. Interestingly, however, LMP2A(+), Btk(-/-) animals produce B cells at a vastly reduced level compared to Btk(-/-) littermates, indicating that LMP2A affects B cell development in the absence of Btk. In the RAG-1(-/-), Btk(-/-) double knockout background, LMP2A is still capable of enhancing the survival of Ig-receptorless B cells. Use of Btk phosphopeptide-specific antibodies reveals that Btk is constitutively phosphorylated in LMP2A-expressing cell lines. These data indicate that LMP2A initiates both Btk-dependent and Btk-independent pathways, resulting in altered B cell development and enhanced B cell survival.
- Northwestern University Philippines
- Northwestern University Medical School United States
- Northwestern University United States
- NORTHWESTERN UNIVERSITY
Male, tyrosine kinases, Herpesvirus 4, Human, Gene Expression, Mice, Transgenic, transgenic mice, Viral Matrix Proteins, Mice, LMP2A, EBV, Virology, Agammaglobulinaemia Tyrosine Kinase, Animals, Humans, Phosphorylation, latency, Homeodomain Proteins, Mice, Knockout, Protein-Tyrosine Kinases, Flow Cytometry, Phenotype, Female, signal transduction, knockout mice, Signal Transduction
Male, tyrosine kinases, Herpesvirus 4, Human, Gene Expression, Mice, Transgenic, transgenic mice, Viral Matrix Proteins, Mice, LMP2A, EBV, Virology, Agammaglobulinaemia Tyrosine Kinase, Animals, Humans, Phosphorylation, latency, Homeodomain Proteins, Mice, Knockout, Protein-Tyrosine Kinases, Flow Cytometry, Phenotype, Female, signal transduction, knockout mice, Signal Transduction
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