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

Background

T_H2 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.

Objective

We investigated IL-13 receptor (IL-13R) expression and regulation in mature and immature human B cells.

Methods

Purified 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.

Results

IL13Rα1 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.

Conclusions

There 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 implications

This 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.

Key words: Human B lymphocyte, IgE regulation, IL-13 receptor

Abbreviations used: APC, Allophycocyanin, BCR, B-cell receptor, CD40L, CD40 ligand, FITC, Fluorescein isothiocyanate, γc, Common γ chain, IL-4R, IL-4 receptor, IL-13R, IL-13 receptor, STAT, Signal transducer and activator of transcription