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.