Regulation of IL-13 receptor α1 expression and signaling on human tonsillar B-lymphocyte subsets

BackgroundTH2 cytokines play crucial roles in driving human B lymphocytes to produce IgE. However, it is unclear whether IL-4 and IL-13 have parallel or sequential roles in the development of B lymphocytes.ObjectiveWe investigated IL-13 receptor (IL-13R) expression and regulation in mature and immature human B cells.MethodsPurified B cells were isolated from human tonsils. We evaluated IL-13Rα1 mRNA expression using real-time PCR and IL-13Rα1 and IL-4 receptor (IL-4R) α expression using flow cytometry and microscopy. Signal transduction was assessed on the basis of signal transducer and activator of transcription 6 phosphorylation.ResultsIL13Rα1 mRNA was induced after stimulation with anti-CD40 antibodies, anti-CD40 plus IL-4, or anti-IgM/IgG. Baseline surface IL13Rα1 levels were low in unstimulated B cells but increased significantly at 24 hours and were sustained for 5 to 14 days. In contrast, IL4Rα was constitutively expressed on tonsillar B cells, and levels did not significantly vary after stimulation. B cells activated by CD40 ligation or B-cell receptor cross-linking, but not resting B cells, showed significant increases in signal transducer and activator of transcription 6 phosphorylation in response to IL-13. IL-13Rα1 expression was induced on mature and memory B cells, as well as on naive subsets.ConclusionsThere is lower constitutive expression and signaling of IL13Rα1 in resting tonsillar B lymphocytes compared with that of IL4Rα. IL-13 is induced on both immature and mature B lymphocytes.Clinical implicationsThis implies different roles for IL-4 and IL-13 in B-cell development, which would allow for specific targeting of IL-13 in IgE-mediated diseases.