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

Abstract: Multiple factors, including expression of costimulatory molecules, antigen-presenting molecules, and target antigens, likely impact the efficacy of antibody therapy and other approaches to the immunotherapy of B cell malignancy. Un-methylated CpG-dinucleotides in select base con-texts (“CpG motifs”) that resemble sequences found in bacterial DNA are potent immunostimu-latory agents capable of inducing a complex im-mune response, including a strong B cell stimulus. We examined the effect of a potent human CpG oligonucleotide (CpG ODN 2006) on different types of primary human malignant B cells and re-active follicular hyperplasia. CpG oligodeoxynu-cleotide (CpG ODN), but not control (non-CpG ODN), increased the expression of costimulatory molecules (CD40, CD80, CD86, CD54) on malig-nant B cells without altering the phenotype of B cells obtained from reactive follicular hyperplasia. CpG ODN also enhanced expression of class I and class II MHC in most samples. CD20 expression was increased in response to CpG ODN, most no-tably in B-CLL and marginal zone lymphoma. An inverse correlation was found between baseline ex-pression of CD20 and CD40 and their expression after exposure to CpG ODN, thus the most signif-icant increase in expression of these molecules was found in those samples that had the lowest baseline levels. In conclusion, CpG ODN can lead to in-creasing expression of molecules involved in co-stimulation, antigen presentation, and as targets for antibody-based therapy and deserve further evaluation as potential immunotherapeutic agents for B cell malignancy. J. Leukoc. Biol. 69: 81–88