First Author | Rowland SL | Year | 2010 |
Journal | J Immunol | Volume | 185 |
Issue | 8 | Pages | 4570-81 |
PubMed ID | 20861359 | Mgi Jnum | J:164719 |
Mgi Id | MGI:4835083 | Doi | 10.4049/jimmunol.1001708 |
Citation | Rowland SL, et al. (2010) BAFF receptor signaling aids the differentiation of immature B cells into transitional B cells following tonic BCR signaling. J Immunol 185(8):4570-81 |
abstractText | BAFF is an important prosurvival cytokine for mature B cells. However, previous studies have shown that BAFFR is already expressed at the immature B cell stage, and that the prosurvival protein Bcl-2 does not completely complement the B cell defects resulting from the absence of BAFFR or BAFF. Thus, we hypothesized that BAFF also functions to aid the differentiation of nonautoreactive immature B cells into transitional B cells and to promote their positive selection. We found that BAFFR is expressed at higher levels on nonautoreactive than on autoreactive immature B cells and that its expression correlates with that of surface IgM and with tonic BCR signaling. Our data indicate that BAFFR signaling enhances the generation of transitional CD23(-) B cells in vitro by increasing cell survival. In vivo, however, BAFFR signaling is dispensable for the generation of CD23(-) transitional B cells in the bone marrow, but it is important for the development of transitional CD23(-) T1 B cells in the spleen. Additionally, we show that BAFF is essential for the differentiation of CD23(-) into CD23(+) transitional B cells both in vitro and in vivo through a mechanism distinct from that mediating cell survival, but requiring tonic BCR signaling. In summary, our data indicate that BAFFR and tonic BCR signals cooperate to enable nonautoreactive immature B cells to differentiate into transitional B cells and to be positively selected into the naive B cell repertoire. |