| First Author | De Silva NS | Year | 2016 |
| Journal | Proc Natl Acad Sci U S A | Volume | 113 |
| Issue | 32 | Pages | 9063-8 |
| PubMed ID | 27457956 | Mgi Jnum | J:235291 |
| Mgi Id | MGI:5796048 | Doi | 10.1073/pnas.1602728113 |
| Citation | De Silva NS, et al. (2016) Transcription factors of the alternative NF-kappaB pathway are required for germinal center B-cell development. Proc Natl Acad Sci U S A 113(32):9063-8 |
| abstractText | The NF-kappaB signaling cascade relays external signals essential for B-cell growth and survival. This cascade is frequently hijacked by cancers that arise from the malignant transformation of germinal center (GC) B cells, underscoring the importance of deciphering the function of NF-kappaB in these cells. The NF-kappaB signaling cascade is comprised of two branches, the canonical and alternative NF-kappaB pathways, mediated by distinct transcription factors. The expression and function of the transcription factors of the alternative pathway, RELB and NF-kappaB2, in late B-cell development is incompletely understood. Using conditional deletion of relb and nfkb2 in GC B cells, we here report that ablation of both RELB and NF-kappaB2, but not of the single transcription factors, resulted in the collapse of established GCs. RELB/NF-kappaB2 deficiency in GC B cells was associated with impaired cell-cycle entry and reduced expression of the cell-surface receptor inducible T-cell costimulator ligand that promotes optimal interactions between B and T cells. Analysis of human tonsillar tissue revealed that plasma cells and their precursors in the GC expressed high levels of NF-kappaB2 relative to surrounding lymphocytes. Accordingly, deletion of nfkb2 in murine GC B cells resulted in a dramatic reduction of antigen-specific antibody-secreting cells, whereas deletion of relb had no effect. These results demonstrate that the transcription factors of the alternative NF-kappaB pathway control distinct stages of late B-cell development, which may have implications for B-cell malignancies that aberrantly activate this pathway. |
