Recruitment mechanisms of primary and malignant B cells to the human liver.
Research output: Contribution to journal › Article
B cells are present within chronically inflamed liver tissue and recent evidence implicates them in the progression of liver disease. In addition a large proportion of hepatic lymphomas are of B cell origin. The molecular signals that regulate normal and malignant B cell recruitment into peripheral tissue from blood are poorly understood leading us to study human B cell migration through hepatic sinusoidal endothelial cells in flow-based adhesion assays. In such assays human blood-derived B cells were captured from shear flow without a prior rolling phase and underwent firm adhesion mediated by VCAM-1. Unlike T cells, which displayed vigorous crawling behaviour on the endothelium, B cells remained static before a proportion underwent transendothelial migration mediated by a combination of ICAM-1, VAP-1, CLEVER-1/stabilin-1 and the chemokine receptors CXCR3 and CXCR4. B cell lymphoma cell lines and primary malignant B cells from patients with chronic lymphocytic leukemia and marginal zone B cell lymphoma also underwent integrin-mediated firm adhesion involving ICAM-1 and/or VCAM-1 and demonstrated ICAM-1 dependent shape-change and crawling behaviour. Unlike primary lymphocytes the malignant cells did not undergo transendothelial migration which could explain why lymphomas are frequently characterised by intravascular accumulation of malignant cells in the hepatic sinusoids. Conclusion: Our findings demonstrate that distinct combinations of signals promote B cell recruitment to the liver suggesting the possibility of novel targets to modulate liver inflammation in disease. Certain features of lymphocyte homing are maintained in lymphoma recruitment to the liver suggesting that therapeutic targets for lymphocyte recruitment may also prevent hepatic lymphoma dissemination. (HEPATOLOGY 2012.).
|Early online date||8 Apr 2012|
|Publication status||Published - 4 Oct 2012|