DEFECTIVE IL-5-RECEPTOR-MEDIATED SIGNALING IN B-CELLS OF X-LINKED IMMUNODEFICIENT MICE

被引:50
作者
KOIKE, M
KIKUCHI, Y
TOMINAGA, A
TAKAKI, S
AKAGI, K
MIYAZAKI, J
YAMAMURA, K
TAKATSU, K
机构
[1] UNIV TOKYO, INST MED SCI, DEPT IMMUNOL, MINATO KU, TOKYO 108, JAPAN
[2] UNIV TOKYO, SCH MED, DEPT DIS RELATED GENE REGULAT RES SANDOZ, BUNKYO KU, TOKYO 113, JAPAN
[3] KUMAMOTO UNIV, SCH MED, INST MOLEC EMBRYOL & GENET, KUMAMOTO 860, JAPAN
关键词
B CELL ACTIVATION; BTK; IL-5 RECEPTOR ALPHA CHAIN; TRANSGENIC MICE; XID;
D O I
10.1093/intimm/7.1.21
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Murine (m) IL-5 induces proliferation and differentiation of both Ly-1(+) B cells and activated conventional B cells, X-linked immunodeficient (XID) mice do not respond to thymus-independent type II antigens, and have an abnormal response to a variety of activation signals through Ig receptors, CD40 and cytokine receptors. Furthermore, XID mice show a B cell specific defect, reflected in decreased numbers of IL-5R alpha(+) B cells and reduced responsiveness of IL-5R alpha(+) B cells to mIL-5. We generated IL-5R alpha transgenic (5R alpha-Tg) mice in which B cells expressed recombinant IL-5R alpha. We crossed male 5R alpha-Tg mice with female XID mice and used their offspring to determine the IL-5 responsiveness of these B cells. All B cells of F-1 male mice carrying the rid gene together with the transgene expressed the recombinant IL-5R alpha. However, those mice lacked Ly-1 B cells and their B cells acquired responsiveness to mIL-5. Interestingly, XID-5R alpha-Tg B cells, but not XID B cells, acquired mIL-5 proliferative and Ig-secretory responsiveness only in the presence of suboptimal doses of lipopolysaccharide. Stimulation of these B cells with mIL-5 plus phorbol myristate acetate induced proliferation, but not Ig secretion. These results indicate that the impaired mIL-5 responsiveness of B cells in XID mice is due to an abnormality of IL-5R-mediated signaling which may correlate with the rid gene mutation, alteration of a single amino acid of Bruton's tyrosine kinase.
引用
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页码:21 / 30
页数:10
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