IL-22, in contrast to IL-10, does not induce Ig production, due to absence of a functional IL-22 receptor on activated human B cells.
IL-22 is an IL-10 homologue that binds to and signals via the class II cytokine receptor (R) heterodimer IL-22RA1/CFR2-4 (IL-10R2), the latter chain being part of the IL-10R complex. Here, we report that, despite its structural similarity with IL-10, as well as its use of the common IL-10R2 chain, IL-22, in contrast to IL-10, is unable to induce Ig production by activated human B cells. Whereas culture of anti-CD40 mAb-stimulated splenic or tonsillar B cells in the presence of rIL-10 resulted in the production of IgG, IgG1, IgG3 and IgA, rIL-22, at concentrations ranging from 4 to 100 ng/ml, did not induce the production of any of these isotypes. Moreover, unlike rIL-10 which enhanced rIL-4-induced IgG4 and IgE production, rIL-22 was ineffective. Although activated B cells expressed transcripts for a soluble IL-22-binding protein (IL-22RA2), no mRNA for a transmembrane IL-22R (IL-22RA1) could be detected. The latter result was confirmed by the demonstration that rIL-22 failed to induce activation of STAT-3 and -5 in resting or activated B cells. Together, these data show that IL-22, in contrast to its homologue IL-10, is not involved in the immunological activity of B cells, which is due to the absence of a functional IL-22R at the surface of these cells.
Lécart
Sandrine
S
INSRM U454, CHU Arnaud de Villeneuve, 371, Avenue Doyen Gaston Giraud, 34295 Montpellier Cedex 5, France.
Morel
Frank
F
Noraz
Nelly
N
Pène
Jérôme
J
Garcia
Martine
M
Boniface
Katia
K
Lecron
Jean-Claude
JC
Yssel
Hans
H
D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D016753:Interleukin-10 / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000097043:Interleukin-22
D007136:Immunoglobulins; D016753:Interleukin-10; D007378:Interleukins; D018123:Receptors, Interleukin; D000097043:Interleukin-22; C415369:interleukin-22 receptor