Defective IL-5-receptor-mediated signaling in B cells of X-linked immunodeficient mice.
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 F1 male mice carrying the xid 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 xid gene mutation, alteration of a single amino acid of Bruton's tyrosine kinase.
Koike
M
M
Department of Immunology, Institute of Medical Science, University of Tokyo, Japan.
Kikuchi
Y
Y
Tominaga
A
A
Takaki
S
S
Akagi
K
K
Miyazaki
J
J
Yamamura
K
K
Takatsu
K
K
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D000955:Antigens, T-Independent / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D007153:Immunologic Deficiency Syndromes / Q000503:physiopathology*; D015848:Interleukin-5 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D018123:Receptors, Interleukin / Q000502:physiology*; D053649:Receptors, Interleukin-5; D015398:Signal Transduction; D014301:Trinitrobenzenes / Q000276:immunology; D014960:X Chromosome
D000955:Antigens, T-Independent; D015848:Interleukin-5; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5; D014301:Trinitrobenzenes; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse