TY - JOUR
T1 - CpG DNA increases primary malignant B cell expression of costimulatory molecules and target antigens
AU - Jahrsdörfer, Bernd
AU - Hartmann, Gunther
AU - Racila, Emil
AU - Jackson, Wallen
AU - Mühlenhoff, Lars
AU - Meinhardt, Gerold
AU - Endres, Stefan
AU - Link, Brian K.
AU - Krieg, Arthur M.
AU - Weiner, George J.
PY - 2001
Y1 - 2001
N2 - 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. 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 oligonucleotide (CpG ODN 2006) on different types of primary human malignant B cells and reactive follicular hyperplasia. CpG of oligodeoxynucleotide (CpG ODN), but not control (non-CpG ODN), increased the expression of costimulatory molecules (CD40, CD80, CD86, CD54) on malignant 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 notably in B-CLL and marginal zone lymphoma. An inverse correlation was found between baseline expression of CD20 and CD40 and their expression after exposure to CpG ODN, thus the most significant increase in expression of these molecules was found in those samples that had the lowest baseline levels. In conclusion, CpG ODN can lead to increasing 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.
AB - 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. 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 oligonucleotide (CpG ODN 2006) on different types of primary human malignant B cells and reactive follicular hyperplasia. CpG of oligodeoxynucleotide (CpG ODN), but not control (non-CpG ODN), increased the expression of costimulatory molecules (CD40, CD80, CD86, CD54) on malignant 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 notably in B-CLL and marginal zone lymphoma. An inverse correlation was found between baseline expression of CD20 and CD40 and their expression after exposure to CpG ODN, thus the most significant increase in expression of these molecules was found in those samples that had the lowest baseline levels. In conclusion, CpG ODN can lead to increasing 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.
KW - B cell activation
KW - CLL
KW - Follicular hyperplasia
KW - Monoclonal antibodies
KW - Non-Hodgkin lymphoma
KW - ODN
UR - http://www.scopus.com/inward/record.url?scp=0035155134&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035155134&partnerID=8YFLogxK
M3 - Article
C2 - 11200072
AN - SCOPUS:0035155134
SN - 0741-5400
VL - 69
SP - 81
EP - 88
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 1
ER -