A soluble form of IL-13 receptor alpha 1 promotes IgG2a and IgG2b production by murine germinal center B cells.
A functional IL-13R involves at least two cell surface proteins, the IL-13R alpha 1 and IL-4R alpha. Using a soluble form of the murine IL-13R alpha 1 (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 alpha 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-13R alpha 1 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.
Department of Immunology, Serono Pharmaceutical Research Institute, Geneva, Switzerland.
J
J
Poudrier
P
P
Graber
S
S
Herren
D
D
Gretener
G
G
Elson
C
C
Berney
J F
JF
Gauchat
M H
MH
Kosco-Vilbois
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D002478:Cells, Cultured; D005260:Female; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D007279:Injections, Subcutaneous; D018793:Interleukin-13 / Q000502:physiology*; D053661:Interleukin-13 Receptor alpha1 Subunit; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D018123:Receptors, Interleukin / Q000008:administration & dosage / Q000378:metabolism / Q000502:physiology*; D053660:Receptors, Interleukin-13; D012995:Solubility
C508183:Il13ra1 protein, mouse; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D015850:Interleukin-6; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13