| First Author | Acosta-Rodríguez EV | Year | 2007 |
| Journal | Eur J Immunol | Volume | 37 |
| Issue | 4 | Pages | 990-1000 |
| PubMed ID | 17357108 | Mgi Jnum | J:120803 |
| Mgi Id | MGI:3708030 | Doi | 10.1002/eji.200636698 |
| Citation | Acosta-Rodriguez EV, et al. (2007) BAFF and LPS cooperate to induce B cells to become susceptible to CD95/Fas-mediated cell death. Eur J Immunol 37(4):990-1000 |
| abstractText | Microorganisms with pathogen-associated molecular patterns (PAMP) activate B cells directly by binding to TLR and also indirectly by inducing APC to release cytokines such as BAFF that promote B cell survival. We found that murine B cells activated concomitantly with LPS (TLR-4 ligand) and BAFF are protected from spontaneous apoptosis, but are more susceptible to Fas/CD95-mediated cell death. This increased susceptibility to Fas-induced apoptosis is associated with a dramatic coordinated up-regulation of Fas/CD95 and IRF-4 expression through a mechanism mediated, at least in part, by inhibition of the MEK/ERK pathway. Up-regulation of Fas/CD95 by BAFF is restricted to B cells activated through TLR-4, but not through TLR-9, BCR or CD40. TLR ligands differ in the BAFF family receptors (R) they induce on B cells: BAFF-R is increased by the TLR4 ligand, LPS, but not by the TLR9 ligand, CpG-containing oligodeoxynucleotides, which, in contrast, strongly up-regulates transmembrane activator and CAML interactor (TACI). This suggests the up-regulation of Fas by BAFF is mediated by BAFF-R and not by TACI. Consistently, APRIL, which binds to TACI and B cell maturation antigen but not BAFF-R, did not enhance Fas expression on LPS-activated B cells. Increased susceptibility to Fas-mediated killing of B cells activated with LPS and BAFF may be a fail-safe mechanism to avoid overexpansion of nonspecific or autoreactive B cells. |
