CLL clones exhibit differential responses to TLR and NOD2 stimulation depending on their IGHV gene mutational status. (A) Induction of CD25 and CD86 after stimulation of all functional receptors tested here (TLR1/2, TLR2/6, TLR7, TLR9 and NOD2). The graph shows median values (before statistical analysis values were normalized to the unstimulated controls). C, CpG ODN; P, Pam3CSK4; M (in x axis), MALP-2; MD, MDP; I, imiquimod; ***p < 0.001. Mutated cases (M [in upper corner]) are indicated in grey; unmutated cases (UM) are indicated in black. (B) TLR1/2, TLR2/6, TLR7 and TLR9 differentially regulate CLL cell apoptosis in mutated-CLL (M) versus unmutated-CLL (UM). Results from flow cytometry analysis for two representative cases are shown. CTL, control; IM, imiquimod; CpG, CpG ODN; PAM, Pam3CSK4; MALP, MALP-2.