Regulation of IL-13 receptor alpha 1 expression and signaling on human tonsillar B-lymphocyte subsets.
BACKGROUND
T(H)2 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-13Ralpha1 mRNA expression using real-time PCR and IL-13Ralpha1 and IL-4 receptor (IL-4R) alpha expression using flow cytometry and microscopy. Signal transduction was assessed on the basis of signal transducer and activator of transcription 6 phosphorylation.


RESULTS
IL13Ralpha1 mRNA was induced after stimulation with anti-CD40 antibodies, anti-CD40 plus IL-4, or anti-IgM/IgG. Baseline surface IL13Ralpha1 levels were low in unstimulated B cells but increased significantly at 24 hours and were sustained for 5 to 14 days. In contrast, IL4R alpha 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-13Ralpha1 expression was induced on mature and memory B cells, as well as on naive subsets.


CONCLUSIONS
There is lower constitutive expression and signaling of IL13Ralpha1 in resting tonsillar B lymphocytes compared with that of IL4R alpha. IL-13 is induced on both immature and mature B lymphocytes.


CONCLUSIONS
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.
Hajoui
Oumnia
O
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Zheng
Huaien
H
Guay
Julie
J
Letuve
Severine
S
Fawaz
Lama M
LM
Mazer
Bruce D
BD
D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D053661:Interleukin-13 Receptor alpha1 Subunit / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D010766:Phosphorylation; D050800:STAT6 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
D053661:Interleukin-13 Receptor alpha1 Subunit; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015847:Interleukin-4