Regulation of IL-13 receptor alpha 1 expression and signaling on human tonsillar B-lymphocyte subsets.
J Allergy Clin Immunol
; 120(6): 1425-32, 2007 Dec.
Article
en En
| MEDLINE
| ID: mdl-17761275
ABSTRACT
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. 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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tonsila Palatina
/
Transducción de Señal
/
Regulación de la Expresión Génica
/
Subgrupos de Linfocitos B
/
Subunidad alfa1 del Receptor de Interleucina-13
Límite:
Humans
Idioma:
En
Revista:
J Allergy Clin Immunol
Año:
2007
Tipo del documento:
Article
País de afiliación:
Canadá