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

Publication ,  Journal Article
Zhang, H; Rosenberg, S; Coffey, FJ; He, Y-W; Manser, T; Hardy, RR; Zhang, J
Published in: J Immunol
January 1, 2009

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.

Duke Scholars

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

January 1, 2009

Volume

182

Issue

1

Start / End Page

207 / 215

Location

United States

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 9
  • Mice, Transgenic
  • Mice, Knockout
  • Mice
  • Immunology
  • Hematopoietic Stem Cells
  • Cell Proliferation
  • Cell Differentiation
  • CASP8 and FADD-Like Apoptosis Regulating Protein
 

Citation

APA
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ICMJE
MLA
NLM
Zhang, H., Rosenberg, S., Coffey, F. J., He, Y.-W., Manser, T., Hardy, R. R., & Zhang, J. (2009). A role for cFLIP in B cell proliferation and stress MAPK regulation. J Immunol, 182(1), 207–215. https://doi.org/10.4049/jimmunol.182.1.207
Zhang, Haibing, Stephen Rosenberg, Francis J. Coffey, You-Wen He, Timothy Manser, Richard R. Hardy, and Jianke Zhang. “A role for cFLIP in B cell proliferation and stress MAPK regulation.J Immunol 182, no. 1 (January 1, 2009): 207–15. https://doi.org/10.4049/jimmunol.182.1.207.
Zhang H, Rosenberg S, Coffey FJ, He Y-W, Manser T, Hardy RR, et al. A role for cFLIP in B cell proliferation and stress MAPK regulation. J Immunol. 2009 Jan 1;182(1):207–15.
Zhang, Haibing, et al. “A role for cFLIP in B cell proliferation and stress MAPK regulation.J Immunol, vol. 182, no. 1, Jan. 2009, pp. 207–15. Pubmed, doi:10.4049/jimmunol.182.1.207.
Zhang H, Rosenberg S, Coffey FJ, He Y-W, Manser T, Hardy RR, Zhang J. A role for cFLIP in B cell proliferation and stress MAPK regulation. J Immunol. 2009 Jan 1;182(1):207–215.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

January 1, 2009

Volume

182

Issue

1

Start / End Page

207 / 215

Location

United States

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 9
  • Mice, Transgenic
  • Mice, Knockout
  • Mice
  • Immunology
  • Hematopoietic Stem Cells
  • Cell Proliferation
  • Cell Differentiation
  • CASP8 and FADD-Like Apoptosis Regulating Protein