Immune Netw.  2018 Feb;18(1):e10. 10.4110/in.2018.18.e10.

Toll-like Receptor 1/2 Agonist Pam3CSK4 Suppresses Lipopolysaccharide-driven IgG1 Production while Enhancing IgG2a Production by B Cells

• Lee SH
• Park SR

• KMID: 2404892
• DOI: http://doi.org/10.4110/in.2018.18.e10

Abstract

Interaction between pathogen-associated molecular patterns and pattern recognition receptors triggers innate and adaptive immune responses. Several studies have reported that toll-like receptors (TLRs) are involved in B cell proliferation, differentiation, and Ig class switch recombination (CSR). However, roles of TLRs in B cell activation and differentiation are not completely understood. In this study, we investigated the direct effect of stimulation of TLR1/2 agonist Pam3CSK4 on mouse B cell viability, proliferation, activation, Ig production, and Ig CSR in vitro. Treatment with 0.5 µg/ml of Pam3CSK4 only barely induced IgG1 production although it enhanced B cell viability. In addition, high-dosage Pam3CSK4 diminished IgG1 production in a dose-dependent manner, whereas the production of other Igs, cell viability, and proliferation increased. Pam3CSK4 additively increased TLR4 agonist lipopolysaccharide (LPS)-induced mouse B cell growth and activation. However, interestingly, Pam3CSK4 abrogated LPS-induced IgG1 production but enhanced LPS-induced IgG2a production. Further, Pam3CSK4 decreased LPS-induced germline γ1 transcripts (GLTγ1)/GLTε expression but increased GLTγ2a expression. On the other hand, Pam3CSK4 had no effect on LPS-induced plasma cell differentiation. Taken together, these results suggest that TLR1/2 agonist Pam3CSK4 acts as a potent mouse B cell mitogen in combination with TLR4 agonist LPS, but these 2 different TLR agonists play diverse roles in regulating the Ig CSR of each isotype, particularly IgG1/IgE and IgG2a.

Keyword

B cells; Toll-like receptor; IgG1; IgG2a; IgE; Class switching

MeSH Terms

Animals
B-Lymphocytes*
Cell Proliferation
Cell Survival
Hand
Immunoglobulin Class Switching
Immunoglobulin E
Immunoglobulin G*
In Vitro Techniques
Mice
Pathogen-Associated Molecular Pattern Molecules
Plasma Cells
Receptors, Pattern Recognition
Recombination, Genetic
Toll-Like Receptors*
Immunoglobulin E
Immunoglobulin G
Pathogen-Associated Molecular Pattern Molecules
Receptors, Pattern Recognition
Toll-Like Receptors