Cutting edge: IL-21 and TLR signaling regulate germinal center responses in a B cell-intrinsic manner.
IL-21 produced by follicular Th (Tfh) cells is an important regulator of Tfh cell development and B cell responses, including germinal center (GC) formation. However, whether defective GC formation and Ab responses are a consequence of impaired Tfh cells development or a B cell-intrinsic defect in IL-21-deficient mice requires clarification. To address this question, we generated chimeric mice lacking IL-21R exclusively on B cells. In this study, we demonstrate that GC reaction and B cell responses induced by immunization with virus-like particles were strongly reduced in both global and B cell-specific IL-21R-deficient mice. Interestingly, the presence of TLR7 ligand within virus-like particles largely restored defective GC reaction and Ab responses in global as well as in B cell-specific IL-21R-deficient mice. Hence, IL-21 acts directly on B cells and cooperates with TLR signaling for optimal B cell responses.
Bessa
Juliana
J
Cytos Biotechnology, Wagistrasse 25, Schlieren 8952, Switzerland.
Kopf
Manfred
M
Bachmann
Martin F
MF
D017908:Allolevivirus / Q000235:genetics / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D015967:Gene Expression Regulation, Viral / Q000276:immunology; D015686:Gene Products, env / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D018858:Germinal Center / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D007113:Immunity, Innate / Q000235:genetics; D007074:Immunoglobulin G / Q000096:biosynthesis; D007378:Interleukins / Q000378:metabolism / Q000502:physiology*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053655:Receptors, Interleukin-21 / Q000172:deficiency / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism / Q000821:virology; D051199:Toll-Like Receptor 7 / Q000378:metabolism / Q000502:physiology*; D051200:Toll-Like Receptor 8 / Q000378:metabolism / Q000502:physiology*; D014771:Virion / Q000235:genetics / Q000276:immunology; D000098546:Interleukin-21
D000914:Antibodies, Viral; D018984:Epitopes, T-Lymphocyte; D015686:Gene Products, env; D007074:Immunoglobulin G; D007378:Interleukins; D008024:Ligands; D008562:Membrane Glycoproteins; D053655:Receptors, Interleukin-21; D011994:Recombinant Proteins; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D000098546:Interleukin-21