Abstract
BackgroundHuman B cells and plasmacytoid dendritic cells (pDC) are the only cells known to express both TLR7 and TLR9. Plasmacytoid dendritic cells are the primary IFN-α producing cells in response to TLR7 and TLR9 agonists. The direct effects of TLR7 stimulation on human B cells is less understood. The objective of this study was to compare the effects of TLR7 and TLR9 stimulation on human B cell function.ResultsGene expression and protein production of cytokines, chemokines, various B cell activation markers, and immunoglobulins were evaluated. Purified human CD19+ B cells (99.9%, containing both naïve and memory populations) from peripheral blood were stimulated with a TLR7-selective agonist (852A), TLR7/8 agonist (3M-003), or TLR9 selective agonist CpG ODN (CpG2006). TLR7 and TLR9 agonists similarly modulated the expression of cytokine and chemokine genes (IL-6, MIP1 alpha, MIP1 beta, TNF alpha and LTA), co-stimulatory molecules (CD80, CD40 and CD58), Fc receptors (CD23, CD32), anti-apoptotic genes (BCL2L1), certain transcription factors (MYC, TCFL5), and genes critical for B cell proliferation and differentiation (CD72, IL21R). Both agonists also induced protein expression of the above cytokines and chemokines. Additionally, TLR7 and TLR9 agonists induced the production of IgM and IgG. A TLR8-selective agonist was comparatively ineffective at stimulating purified human B cells.ConclusionThese results demonstrate that despite their molecular differences, the TLR7 and TLR9 agonists induce similar genes and proteins in purified human B cells.
Highlights
Human B cells and plasmacytoid dendritic cells are the only cells known to express both TLR7 and TLR9
B cell purity and Toll-like receptors (TLRs) basal gene expression B cells were enriched from human peripheral blood mononuclear cells (PBMCs) by negative selection and purified by cell sorting
The B cells expressed intermediate to high levels of TLR6, TLR7, TLR9, and TLR10, and about 10-fold lower levels of TLR2 and TLR4
Summary
Human B cells and plasmacytoid dendritic cells (pDC) are the only cells known to express both TLR7 and TLR9. The direct effects of TLR7 stimulation on human B cells is less understood. The objective of this study was to compare the effects of TLR7 and TLR9 stimulation on human B cell function. Through ligand receptor signaling they differentiate into specialized cells capable of communicating with helper T cells in order to undergo antibody diversification, clonal expansion and immunoglobulin secretion. Various ligands and their corresponding receptors are responsible for these signaling events leading towards B cell activation and maturation. Among recently discovered B cell activators, of particular interest are the Toll-like receptors (TLRs) and their natural agonists responsible for eliciting direct effects on human (page number not for citation purposes). The copy number for TLR2 to TLR10 mRNA was normalized to that for GAPDH to compare expression between donors
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