Overexpression of Bcl-2 does not rescue impaired B lymphopoiesis in IL-7 receptor-deficient mice but can enhance survival of mature B cells.
IL-7 receptor-deficient (IL-7R(-/-)) mice are lymphopenic as a result of defective cell production at early steps in both B and T lymphopoiesis. In the bone marrow, there is an incomplete block in B cell development at the transition from the pro-B to the pre-B cell stage. As a consequence, peripheral lymphoid organs of IL-7R(-/-) mice contain abnormally low numbers of mature surface (s) Ig-expressing B cells and this is accompanied by a relative increase in immature sIg- B cells. Transgenic expression of the anti-apoptotic protein Bcl-2 in IL-7R(-/-) mice rescues the defect in T cell development and in mature T cell function. The present report shows that constitutive expression of Bcl-2 is incapable of rescuing B lymphopoiesis in IL-7R(-/-) mice but can enhance survival of those mature B cells which escape the developmental arrest. Thus the essential role of IL-7R signaling in B lymphoid cells cannot be replaced by Bcl-2, indicating that in B lymphopoiesis IL-7R signaling is necessary for promoting cell division and/or for inhibiting a Bcl-2-insensitive pathway to apoptosis.
Maraskovsky
E
E
Department of Immunobiology, Immunex Corp., Seattle, WA 98101, USA.
Peschon
J J
JJ
McKenna
H
H
Teepe
M
M
Strasser
A
A
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D005260:Female; D015870:Gene Expression; D006410:Hematopoiesis / Q000502:physiology*; D008221:Lymphoid Tissue / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D020395:Receptors, Interleukin-7 / Q000172:deficiency* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013268:Stimulation, Chemical; D019076:Transgenes
D008934:Mitogens; D019253:Proto-Oncogene Proteins c-bcl-2; D020395:Receptors, Interleukin-7