title: IL-21 enhances the activity of the TLR-MyD88-STAT3 pathway but not the classical TLR-MyD88-NF-κB pathway in human B cells to boost antibody production.
abstract: Both IL-21 and TLR agonists are important regulators of B cell responses, and the combination of IL-21 and TLR stimulation results in increased Ab production. However, it is not clear yet how IL-21 interacts with TLR signaling in B cells. In this study, we show that IL-21 enhances TLR-induced IgG production, whereas it has no effect on TLR-induced IL-6 production by human B cell cultures. These observations are explained by the finding that IL-21 augments TLR-induced IgG production via the TLR-MyD88-STAT3 pathway but not the classical TLR-MyD88-NF-κB pathway. We further demonstrate that stimulation of human B cells with IL-21 and TLR7/8 or TLR9 agonists increases the phosphorylation of STAT3, whereas the activation of NF-κB is not affected. Interestingly, like IL-21, IL-10 in combination with TLR signaling also enhances phosphorylation of STAT3, resulting in an increase of IgG production. Hence, IL-21 and IL-10 increase the activity of the TLR-MyD88-STAT3 pathway in human B cells via enhancing the phosphorylation of STAT3 for Ab production.
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, 2300RC Leiden, The Netherlands.
authors.forename: Bi-Sheng
authors.initials: BS
authors.lastname: Liu
authors.forename: Jeroen N
authors.initials: JN
authors.lastname: Stoop
authors.forename: Tom W
authors.initials: TW
authors.lastname: Huizinga
authors.forename: Rene E M
authors.initials: RE
authors.lastname: Toes
mesh_terms: D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis; D007378:Interleukins / Q000819:agonists / Q000378:metabolism*; D008213:Lymphocyte Activation; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012097:Repressor Proteins / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D051199:Toll-Like Receptor 7 / Q000819:agonists / Q000276:immunology; D051200:Toll-Like Receptor 8 / Q000819:agonists / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000819:agonists / Q000276:immunology; D000098546:Interleukin-21
chemical_list: D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015850:Interleukin-6; D007378:Interleukins; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C495348:TLR7 protein, human; C495349:TLR8 protein, human; C495371:TLR9 protein, human; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D051217:Toll-Like Receptor 9; D016753:Interleukin-10; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1; D000098546:Interleukin-21