Defective IL-5-receptor-mediated signaling in B cells of X-linked immunodeficient mice

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-5Rtransgenic (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.