Format:
Online-Ressource
ISSN:
1521-4141
Content:
Abstract: 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.
In:
volume:37
In:
number:4
In:
year:2007
In:
pages:990-1000
In:
extent:11
In:
European journal of immunology, Weinheim : Wiley-VCH, 1971-, 37, Heft 4 (2007), 990-1000 (gesamt 11), 1521-4141
Language:
English
DOI:
10.1002/eji.200636698
URN:
urn:nbn:de:101:1-2023062807215070182989
URL:
https://doi.org/10.1002/eji.200636698
URL:
https://nbn-resolving.org/urn:nbn:de:101:1-2023062807215070182989
URL:
https://d-nb.info/1294203029/34
URL:
https://doi.org/10.1002/eji.200636698
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