The CD5 molecule, a pan-T lymphocyte marker, is present on an uncommon subset of circulating B lymphocytes. In human beings, the subset of CD5+ B cells is the proliferative component in chronic lymphocytic leukemia and may be responsible for a variety of auto-immune diseases. Cattle infected with bovine leukemia virus, an oncornavirus which is structurally similar to HTLV-I, often develop persistent lymphocytosis, a non-neoplastic polyclonal expansion of CD5+ B cells. These animals offer a source of numerous CD5+ B cells for biochemical analysis, as well as being an animal model of a naturally occurring disease involving proliferation of this cellular subset. In T cells, the CD5 molecule is linked to known signal receptors and transducers and also binds to signal receptors on B cells. Despite these advances in understanding of the role of CD5 as a signalling molecule in T cells, its role in B cells is poorly elucidated. By analogy with T cells, it is likely that the CD5 molecule in B cells is important in both intra- and intercellular signalling. In this proposal, the goal is to characterize the interactions of the CD5 molecule in B cells from BLV-infected persistently lymphocytotic cattle.
The specific aims are to: (1) Identify molecules which are physically linked to CD5 and determine if these molecules are protein kinases, (2) Identify molecules which act as ligands of B cell CD5, and (3) Identify and characterize domains of the CD5 molecule which interact with molecules identified in Aims 1 and 2.
| Cantor, G H; Pritchard, S M; Dequiedt, F et al. (2001) CD5 is dissociated from the B-cell receptor in B cells from bovine leukemia virus-infected, persistently lymphocytotic cattle: consequences to B-cell receptor-mediated apoptosis. J Virol 75:1689-96 |
| Cantor, G H; Pritchard, S M; Orlik, O et al. (1999) Bovine leukemia virus transmembrane protein gp30 physically associates with the down-regulatory phosphatase SHP-1. Cell Immunol 193:117-24 |
| Davis, W C; Naessens, J; Brown, W C et al. (1996) Analysis of monoclonal antibodies reactive with molecules upregulated or expressed only on activated lymphocytes. Vet Immunol Immunopathol 52:301-11 |
| Cantor, G H (1996) A potential proline-rich motif upstream of the immunoreceptor tyrosine-based activation motif in bovine leukemia virus gp30, Epstein-Barr virus LMP2A, herpesvirus papio LMP2A, and African horsesickness virus VP7. Virology 220:265-6 |
