| First Author | De Silva NS | Year | 2016 |
| Journal | J Immunol | Volume | 196 |
| Issue | 6 | Pages | 2591-601 |
| PubMed ID | 26851215 | Mgi Jnum | J:233743 |
| Mgi Id | MGI:5787980 | Doi | 10.4049/jimmunol.1501120 |
| Citation | De Silva NS, et al. (2016) Impairment of Mature B Cell Maintenance upon Combined Deletion of the Alternative NF-kappaB Transcription Factors RELB and NF-kappaB2 in B Cells. J Immunol 196(6):2591-601 |
| abstractText | BAFF is critical for the survival and maturation of mature B cells. BAFF, via BAFFR, activates multiple signaling pathways in B cells, including the alternative NF-kappaB pathway. The transcription factors RELB and NF-kappaB2 (p100/p52) are the downstream mediators of the alternative pathway; however, the B cell-intrinsic functions of these NF-kappaB subunits have not been studied in vivo using conditional alleles, either individually or in combination. We in this study report that B cell-specific deletion of relb led to only a slight decrease in the fraction of mature splenic B cells, whereas deletion of nfkb2 caused a marked reduction. This phenotype was further exacerbated upon combined deletion of relb and nfkb2 and most dramatically affected the maintenance of marginal zone B cells. BAFF stimulation, in contrast to CD40 activation, was unable to rescue relb/nfkb2-deleted B cells in vitro. RNA-sequencing analysis of BAFF-stimulated nfkb2-deleted versus normal B cells suggests that the alternative NF-kappaB pathway, in addition to its critical role in BAFF-mediated cell survival, may control the expression of genes involved in the positioning of B cells within the lymphoid microenvironment and in the establishment of T cell-B cell interactions. Thus, by ablating the downstream transcription factors of the alternative NF-kappaB pathway specifically in B cells, we identify in this study a critical role for the combined activity of the RELB and NF-kappaB2 subunits in B cell homeostasis that cannot be compensated for by the canonical NF-kappaB pathway under physiological conditions. |
