NF-kappaB inducible genes BCL-X and cyclin E promote immature B-cell proliferation and survival.
B-cell receptor (BCR) ligation induces proliferation and survival in mature B-cells but conversely, can lead to apoptosis in immature B-cells. We have previously shown that c-Rel, a member of the NF-kappaB transcription factor family, is essential for mature B-cell survival and proliferation via regulation of the anti-apoptotic molecule Bcl-X and cell cycle genes E2F3a and cyclin E. Here, we report that c-Rel-deficient mature B-cells are rendered sensitive to BCR-induced growth arrest and apoptosis in a manner that strongly resembles the phenotypic response of immature B-cells to BCR signaling. We further demonstrate that BCR-stimulated immature B-cells are defective in NF-kappaB activation, but that introduction of two downstream c-Rel target genes, Bcl-X and cyclin E, can restore survival and proliferation to these cells. Our studies therefore suggest that specific blockade of NF-kappaB activation may be responsible for the growth arrest and apoptosis of BCR-activated immature B-cells.
Feng
Biao
B
Division of Immunology, Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.
Cheng
Shuhua
S
Hsia
Constance Yu
CY
King
Leslie B
LB
Monroe
John G
JG
Liou
Hsiou-Chi
HC
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D003433:Crosses, Genetic; D019927:Cyclin E / Q000187:drug effects / Q000235:genetics* / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D020573:Genes, rel / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000235:genetics* / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000037:antagonists & inhibitors / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D019927:Cyclin E; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D011947:Receptors, Antigen, B-Cell; D051020:bcl-X Protein