Defective IL-5-receptor-mediated signaling in B cells of X-linked immunodeficient mice |
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Authors: | Koike, Masamichi Kikuchi, Yuji Tominaga, Akira Takaki, Satoshi Akagi, Kiwamu Miyazaki, Jun-ichi Yamamura, Ken-ichi Takatsu, Kiyoshi |
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Affiliation: | 1 Department of Immunology, Institute of Medical Science, University of Tokyo 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan 2 Department of Disease-related Gene Regulation Research (Sandoz), School of Medicine, University of Tokyo 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan 3 Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine 2-2-1 Honjo, Kumamoto 860, Japan 4Present address: Kyowa Hakko Kogyo Co., Ltd, 3-6-6 Asahi-machi, Machida-shi, Tokyo 194, Japan |
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Abstract: | Murine (m) IL-5 induces proliferation and differentiation ofboth Ly-1+; B cells and activated conventional B cells. X-linkedimmunodeficient (XID) mice do not respond to thymus-independenttype II antigens, and have an abnormal response to a varietyof activation signals through Ig receptors, CD40 and cytokinereceptors. Furthermore, XID mice show a B cell specific defect,reflected in decreased numbers of IL-5R + B cells and reducedresponsiveness of IL-5R + B cells to mIL-5. We generated IL-5R transgenic (5R -Tg) mice in which B cells expressed recombinantIL-5R . We crossed male 5R -Tg mice with female XID mice and usedtheir offspring to determine the IL-5 responsiveness of theseB cells. All B cells of F1 male mice carrying the xid gene togetherwith the transgene expressed the recombinant IL-5R . However,those mice lacked Ly-1 B cells and their B cells acquired responsivenessto mIL-5. Interestingly, XID-5R -Tg B cells, but not XID B cells,acquired mIL-5 proliferatlve and Ig-secretory responsivenessonly in the presence of suboptimal doses of Ilpopolysaccharide.Stimulation of these B cells with mIL-5 plus phorbol myristateacetate induced proliferation, but not Ig secretion. These resultsindicate that the impaired mIL-5 responsiveness of B cells inXID mice is due to an abnormality of IL-5R-mediated signalingwhich may correlate with the xid gene mutation, alteration ofa single amino acid of Bruton's tyroslne kinase. |
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Keywords: | B cell activation Btk IL-5 receptor /math/alpha.gif" ALT=" {alpha}" BORDER=" 0" > chain transgenic mice XID |
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