Article
Dissecting the chemokine-driven spread of B cell lymphoma cells into the central nervous system
Search Medline for
Authors
Published: | September 11, 2012 |
---|
Outline
Text
There is increasing evidence that chemokine gradients specify the organotropism of B cell lymphomas. Specifically, migration to the central nervous system (CNS) appears to be regulated by specific chemokine-chemokine receptor interactions including CXC motif chemokine 13 (CXCL13) and its corresponding receptor CXC motif chemokine receptor 5 (CXCR5) in humans. Ectopic expression of those chemokines is often induced in sites of chronic inflammation.
To investigate the migratory capacity of B cell lymphomas towards inflammatory lesions, transgenic B cell lymphoma-bearing Eu-myc mice were crossed to mice overexpressing CXCL13 in pancreatic islets (RIP-CXCL13+/-). Histological analyses of Eµ-myc;RIP-CXCL13+/- exhibited B cell lymphomas and co-localizing lymphocytes within pancreatic islets. In order to dissect whether B cell lymphoma cells are attracted to CXCL13-rich areas by expression of CXCR5 or indirectly by CXCR5 expression on concomitant lymphocytes, B cell lymphoma cells harbouring wildtype levels of CXCR5 were transferred into RIP-CXCL13 mice deficient for CXCR5. Since the latter displayed no B cell lymphomas in CXCL13-overexpressing pancreatic islets, we can conclude that lymphoma cell migration towards CXCL13-rich areas rather depends on CXCR5-mediated infiltration of lymphocytes, which in turn attract B cell lymphoma cells. This is supported by the finding that almost no B cell lymphomas were detectable in the pancreas upon transfer into RIP-CXCL13 mice crossed to Rag1-/- mice, which lack mature lymphocytes. Based on these findings we are presently pursuing experiments aimed to develop a mouse model displaying a spread of B cell lymphomas into the CNS. Such models will help to dissect the specific chemokine milieu relevant for systemic spread of lymphoma cells in order to identify novel druggable targets aimed at inhibiting lymphoma dissemination.