Translocation of the B cell receptor to lipid rafts is inhibited in B cells from BLV-infected, persistent lymphocytosis cattle.
Bovine leukemia virus (BLV) infection causes a significant polyclonal expansion of CD5(+), IgM+ B lymphocytes known as persistent lymphocytosis (PL) in approximately 30% of infected cattle. There is evidence that this expanded B cell population has altered signaling, and resistance to apoptosis has been proposed as one mechanism of B cell expansion. In human and murine B cells, antigen binding initiates movement of the B cell receptor (BCR) into membrane microdomains enriched in sphingolipids and cholesterol, termed lipid rafts. Lipid rafts include members of the Src-family kinases and exclude certain phosphatases. Inclusion of the BCR into lipid rafts plays an important role in regulation of early signaling events and subsequent antigen internalization. Viral proteins may also influence signaling events in lipid rafts. Here we demonstrate that the largely CD5(+) B cell population in PL cattle has different mobilization and internalization of the BCR when compared to the largely CD5-negative B cells in BLV-negative cattle. Unlike B cells from BLV-negative cattle, the BCR in B cells of BLV-infected, PL cattle resists movement into lipid rafts upon stimulation and is only weakly internalized. Expression of viral proteins as determined by detection of the BLV transmembrane (TM) envelope glycoprotein gp30 did not alter these events in cells from PL cattle. This exclusion of the BCR from lipid rafts may, in part, explain signaling differences seen between B cells of BLV-infected, PL, and BLV-negative cattle and the resistance to apoptosis speculated to contribute to persistent lymphocytosis.
Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA. Valerie_Hamilton@Merck.com
Valerie T
VT
Hamilton
Diana M
DM
Stone
Glenn H
GH
Cantor
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology*; D018956:CD5 Antigens / Q000378:metabolism; D002417:Cattle; D002418:Cattle Diseases / Q000276:immunology / Q000473:pathology / Q000821:virology; D016583:Enzootic Bovine Leukosis / Q000276:immunology / Q000503:physiopathology*; D001909:Leukemia Virus, Bovine / Q000276:immunology / Q000472:pathogenicity*; D008213:Lymphocyte Activation; D008218:Lymphocytosis / Q000503:physiopathology / Q000662:veterinary*; D021962:Membrane Microdomains / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015682:Retroviridae Proteins, Oncogenic / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism
D018956:CD5 Antigens; D011947:Receptors, Antigen, B-Cell; D015682:Retroviridae Proteins, Oncogenic; D014759:Viral Envelope Proteins; C060711:gp30 envelope transmembrane protein, Bovine leukemia virus