The Fas-associated death domain protein is required in apoptosis and TLR-induced proliferative responses in B cells

Hongxia Z. Imtiyaz, Stephen Rosenberg, Yuhang Zhang, Ziaur Rahman, Ying Ju Hou, Tim Manser, Jianke Zhang

Research output: Contribution to journalArticle

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Abstract

The Fas-associated death domain protein (FADD)/Mort1 is a signaling adaptor protein which mediates the activation of caspase 8 during death receptor-induced apoptosis. Disruption of FADD in germ cells results in death receptor-independent embryonic lethality in mice. Previous studies indicated that in addition to its function in apoptosis, FADD is also required in peripheral T cell homeostasis and TCR-induced proliferative responses. In this report, we generated B cell-specific FADD-deficient mice and showed that deletion of FADD at the pro-B cell stage had minor effects on B cell development in the bone marrow, and resulted in increased splenic and lymph node B cell numbers and decreased peritoneal B1 cell numbers. As in T cells, a FADD deficiency inhibited Fas-induced apoptosis in B cells. However, B cell-proliferative responses induced by stimulation of the BCR and CD40 using anti-IgM or anti-CD40 Abs were unaffected by the absence of FADD. Further analyses revealed that FADD-deficient B cells were defective in proliferative responses induced by treatments with dsRNA and LPS which stimulate TLR3 and TLR4, respectively. Therefore, in addition to its apoptotic function, FADD also plays a role in TLR3- and TLR4-induced proliferative responses in B cells.

Original languageEnglish (US)
Pages (from-to)6852-6861
Number of pages10
JournalJournal of Immunology
Volume176
Issue number11
DOIs
StatePublished - Jun 1 2006

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Fas-Associated Death Domain Protein
B-Lymphocytes
Apoptosis
Death Domain Receptors
Cell Count
T-Lymphocytes
Protein Deficiency
B-Lymphoid Precursor Cells
Caspase 8
Germ Cells
Homeostasis
Lymph Nodes
Bone Marrow

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Imtiyaz, Hongxia Z. ; Rosenberg, Stephen ; Zhang, Yuhang ; Rahman, Ziaur ; Hou, Ying Ju ; Manser, Tim ; Zhang, Jianke. / The Fas-associated death domain protein is required in apoptosis and TLR-induced proliferative responses in B cells. In: Journal of Immunology. 2006 ; Vol. 176, No. 11. pp. 6852-6861.
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The Fas-associated death domain protein is required in apoptosis and TLR-induced proliferative responses in B cells. / Imtiyaz, Hongxia Z.; Rosenberg, Stephen; Zhang, Yuhang; Rahman, Ziaur; Hou, Ying Ju; Manser, Tim; Zhang, Jianke.

In: Journal of Immunology, Vol. 176, No. 11, 01.06.2006, p. 6852-6861.

Research output: Contribution to journalArticle

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