The human Burkitt lymphoma cell line Namalwa represents a homogenous cell system characterized by high levels of Toll-like receptor 9 and activation by CpG oligonucleotides.
Human B cells and plasmacytoid dendritic cells constitutively express Toll-like receptor (TLR)9 and respond to TLR9 ligands, as evidenced by nuclear factor kappa B translocation and cytokine secretion. However, TLR9 expression on B lymphocytes appears to be dependent upon both the state of activation and differentiation of the B cell population. In the current study, TLR9 mRNA expression was evaluated in transformed human B cell lines and correlated with their response to CpG. Among the B cell lines, the Burkitt lymphoma-derived Namalwa line had the highest level of TLR9 expression, 20-fold greater than spleen. Following incubation with CpG oligonucleotide, Namalwa cells secreted increased amounts of TNF, IL-6, and IL-10 and expressed the costimulator molecules CD40, CD80, and CD86. These functional responses to TLR9 activation occurred with similar EC(50) values in the 30- to 60-nM range. These results suggest that the Namalwa Burkitt lymphoma line may serve as a useful cell-based assay for the detection of novel TLR9 agonists as well as a model to further explore the regulation of TLR9 expression and signaling.
Henault
Martin
M
Division of Bone and Inflammation Research, Lilly Research Laboratories, Indianapolis, IN, USA.
Lee
Linda N
LN
Evans
Glenn F
GF
Zuckerman
Steven H
SH
D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000235:genetics*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics*; D015398:Signal Transduction; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors
C408982:CPG-oligonucleotide; D016207:Cytokines; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011956:Receptors, Cell Surface; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors