The long-term goal of is to understand the role of Epstein-Barr Virus (EBV) latent membrane protein 2A (LMP2A) in maintaining EBV latency in B cells. The goal of this study is to determine if LMP2A alters B cell survival and function in vivo. Based on previous data, the hypothesis for this study is that LMP2A signals in Ig-bearing B cells to inhibit B cell activation, while promoting B cell survival in vivo. To test this hypothesis, the following aims will be performed: (1) Determine if LMP2A extends the survival of Ig-beadng B cells in vivo in the absence or presence of antigen. (2) Determine if LMP2A inhibits BCR signaling in Ig-bearing B cells induced by autoantigen. (3) Determine if LMP2A inhibits the function of B cells in response to antigen in vivo and in vitro. By crossing transgenic mice that express LMP2A in B cells to mice that produce B cells with BCR specific for hen-egg lysozyme (HEL), we have generated a novel system to test if LMP2A alters B cell survival and activation in vivo. BrdU-labeling, FACS analysis, antibody responses and Western Blot analysis will be utilized to determine if LMP2A alters the half life and activation of Ig-bearing B cells. These studies may provide rationales for therapeutics to eradicate EBV latent infection in B cells that precedes malignant tumors.
| Swanson-Mungerson, Michelle; Longnecker, Richard (2007) Epstein-Barr virus latent membrane protein 2A and autoimmunity. Trends Immunol 28:213-8 |
| Swanson-Mungerson, Michelle; Bultema, Rebecca; Longnecker, Richard (2006) Epstein-Barr virus LMP2A enhances B-cell responses in vivo and in vitro. J Virol 80:6764-70 |
| Swanson-Mungerson, Michelle A; Caldwell, Robert G; Bultema, Rebecca et al. (2005) Epstein-Barr virus LMP2A alters in vivo and in vitro models of B-cell anergy, but not deletion, in response to autoantigen. J Virol 79:7355-62 |
