King's College London

Research portal

Phenotype and immune function of lymph node and peripheral blood CLL cells are linked to transendothelial migration.

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)563-573
Number of pages11
Issue number4
Early online date1 Jun 2016
Publication statusPublished - 28 Jul 2016


King's Authors


Several lines of evidence suggest that homing of tumor cells to lymphoid tissue contributes to disease progression in chronic lymphocytic leukemia (CLL). Here we demonstrate that lymph node (LN)-derived CLL cells possess a distinct phenotype and exhibit enhanced capacity for Tcell activation and superior immune synapse formation when compared to paired peripheral
blood samples (PB). LN-derived CLL cells manifest a proliferative, CXCR4dimCD5bright, phenotype compared to those in the PB and higher expression of T-cell activation molecules including CD80, CD86 and HLA-DR. In addition, LN-CLL cells have higher expression of α4β1 (CD49d) which, as well as being a co-stimulatory molecule, is required for CLL cells to undergo
transendothelial migration (TEM) and enter the proliferation centers of the LNs.
Using an in-vitro system that models circulation and TEM, we showed that the small population of CLL cells that migrate are CXCR4dimCD5bright with higher CD49d, CD80, CD86 and HLA-DR compared to those that remain circulating; a phenotype strikingly similar to LN-derived CLL cells. Furthermore, sorted CD49dhi CLL cells showed enhanced capacity to activate T-cells
compared to CD49dlo sub-populations from the same patient. Thus, although PB-CLL cells have reduced capacity to form immune synapses and activate CD4+ T-cells, this was not the case for LN-CLL cells or those with the propensity to undergo TEM. Taken together, our study suggests that CLL cell immunological function is not only modulated by microenvironmental interactions
but is also a feature of a sub-population of PB-CLL cells that are primed for lymphoid tissue homing and interaction with T-cells.

Download statistics

No data available

View graph of relations

© 2018 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454