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1 Promotes IgG2a and IgG2b Production by Murine Germinal Center B Cells1
*
Department of Immunology, Serono Pharmaceutical Research Institute, Geneva, Switzerland; and
Centre d’Immunologie Pierre Fabre, St. Julien-en-Genevois, France
A functional IL-13R involves at least two cell surface proteins,
the IL-13R
1 and IL-4R. Using a soluble form of the murine
IL-13R1 (sIL-13R), we reveal several novel features of this system.
The sIL-13R promotes proliferation and augmentation of Ag-specific IgM,
IgG2a, and IgG2b production by murine germinal center (GC) B cells in
vitro. These effects were enhanced by CD40 signaling and were not
inhibited by an anti-IL4R mAb, a result suggesting other
ligands. In GC cell cultures, sIL-13R also promoted IL-6 production,
and interestingly, sIL-13R-induced IgG2a and IgG2b augmentation was
absent in GC cells isolated from IL-6-deficient mice. Furthermore, the
effects of the sIL-13R molecule were inhibited in the presence of an
anti-IL-13 mAb, and preincubation of GC cells with IL-13 enhanced
the sIL-13R-mediated effects. When sIL-13R was injected into mice, it
served as an adjuvant-promoting production to varying degrees of IgM
and IgG isotypes. We thus propose that IL-13R1 is a molecule
involved in B cell differentiation, using a mechanism that may involve
regulation of IL-6-responsive elements. Taken together, our data reveal
previously unknown activities as well as suggest that the ligand for
the sIL-13R might be a component of the IL-13R complex or a
counterstructure yet to be defined.
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