A role for cFLIP in B cell proliferation and stress MAPK regulation.

Journal Article (Journal Article)

Fas/Apo-1 signals through the FADD (Fas-associated death domain) adaptor protein, which recruits and activates the apical caspase 8 and leads to apoptosis. Cellular FLIP (cFLIP) is a homolog of caspase 8 and is also capable of binding to FADD. Previous studies suggest that cFLIP could either enhance or inhibit apoptosis and lead to NF-kappaB and Erk1/2 activation. Like FADD or caspase 8 deficiency, a lack of cFLIP disrupts embryogenesis and T cell proliferation. It has been demonstrated that B cells lacking either FADD or caspase 8 were defective in both Fas-induced apoptosis and TLR-induced proliferation, which indicates that these death-inducing proteins have an additional role in regulating innate immunity. To analyze the function of cFLIP in B cells, conditional deletion of cFLIP was induced by using CD19(Cre). The resulting B cell-specific cFLIP-deficient mice were found to have reduced numbers of peripheral B cells that were hypersensitive to Fas-induced apoptosis and impaired in proliferation induced by TLRs and the BCR. Furthermore, there was aberrant expression of costimulatory proteins and activation markers in cFLIP-deficient B cells. Whereas LPS-induced activation of NF-kappaB and Erk1/2 appears to be unaffected, p38 and Jnk were spontaneously activated and hyperinduced in cFLIP-deficient B cells. Therefore, these data revealed novel functions of cFLIP in B cells.

Full Text

Duke Authors

Cited Authors

  • Zhang, H; Rosenberg, S; Coffey, FJ; He, Y-W; Manser, T; Hardy, RR; Zhang, J

Published Date

  • January 1, 2009

Published In

Volume / Issue

  • 182 / 1

Start / End Page

  • 207 - 215

PubMed ID

  • 19109151

Pubmed Central ID

  • PMC2720129

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.182.1.207


  • eng

Conference Location

  • United States