Research article

Comparison of human B cell activation by TLR7 and TLR9 agonists

John A Hanten^1,2 , John P Vasilakos^1,3 , Christie L Riter¹ , Lori Neys^1,4 , Kenneth E Lipson^1,5 , Sefik S Alkan^1,6 and Woubalem Birmachu^1,7

¹Department of Pharmacology, 3M Pharmaceuticals, St. Paul, MN 55144, USA

²3M Drug Delivery Systems, St. Paul, MN 55144, USA

³Biothera, 3388 Mike Collins Dr, Eagan, MN 55121, USA

⁴DiaSorin, 1951 Northwestern Ave, P.O. Box 285, Stillwater MN 55082, USA

⁵FibroGen, Inc., 225 Gateway Blvd., South San Francisco, CA 94080, USA

⁶Alba Therapeutics Corp, 800 W. Baltimore St., Suite 400, Baltimore, MD 21201, USA

⁷3M Medical, St. Paul, MN 55144, USA

author email corresponding author email

BMC Immunology 2008, 9:39doi:10.1186/1471-2172-9-39

Published:	24 July 2008

Abstract

Background

Human 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.

Results

Gene 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.

Conclusion

These results demonstrate that despite their molecular differences, the TLR7 and TLR9 agonists induce similar genes and proteins in purified human B cells.