Expression and function of toll like receptors in chronic lymphocytic leukaemia cells

Mature B-cells can recognize microbial antigens via B-cell-receptor (BCR) in a specific way and via Toll-like receptors (TLR) in a costimulatory manner. A wealth of information is gathering on the possible role of antigenic stimulation in the natural history of Chronic Lymphocytic Leukaemia (CLL). However little is known regarding the repertoire and function of TLR in CLL cells. The TLR family includes 10 different transmembrane proteins devoted to recognize specific pathogen-associated molecular patterns and to alarm immunocompetent cells to trigger an immune response. Here, we studied fresh leukaemic cells for the expression pattern of TLR1 to TLR10, NOD1, NOD2 and SIGIRR (also known as TIR8). CLL cells were found to express several pattern recognition receptors including TLR1, TLR2, TLR6, TLR10, NOD1 and NOD2. The specific TLR expressed by CLL cells were functional. Leukaemic cells, upon stimulation with TLR1/2/6 ligands, such as bacterial lipopeptides, activated the nuclear factor-kappa B signalling pathway, expressed CD86 and CD25 activation molecules, and were protected from spontaneous apoptosis. These findings further support the hypothesis that CLL cells resemble antigen-activated B-cells and suggest a potential role of TLR in modulating CLL cell response in the context of specific antigen recognition.