CpG DNA increases primary malignant B cell expression of costimulatory molecules and target antigens

Multiple factors, including expression of costimulatory molecules, antigen- presenting molecules, and target antigens, likely impact the efficacy of an tibody therapy and other approaches to the immunotherapy of Il cell maligna ncy. Unmethylated CpG-dinucleotides in select base contexts ("CpG motifs") that resemble sequences found in bacterial DNA are potent immunostimulatory agents capable of inducing a complex immune response, including a strong B cell stimulus. We examined the effect of a potent human CpG oligonucleotid e (CpG ODN 2006) on different types of primary human malignant B cells and reactive follicular hyperplasia. CpG oligodeoxynucleotide (CpG ODN), but no t control (non-CpG ODN), increased the expression of costimulatory molecule s (CD40, CD80, CD86, CD54) on malignant B cells without altering the phenot ype of B cells obtained front reactive follicular hyperplasia. CPG ODN also enhanced expression of class I and class II MHC in most samples, CD20 expr ession was increased in response to CpG ODN, most notably in B-CLL and marg inal zone lymphoma. An inverse correlation was found between baseline expre ssion of CD20 ann CD40 and their expression after exposure to CpG ODN, thus the most significant increase ill expression of these molecules was found in those samples that had the lowest baseline levels. In conclusion, CpG OD N call lead to increasing expression of molecules involved in costimulation , antigen presentation, and as targets for antibody-based therapy and deser ve further evaluation as potential immunotherapeutic agents for B cell mali gnancy.