AI Article Synopsis
- BAFF and APRIL are immune mediators that promote class-switch recombination (CSR) in B cells by interacting with the receptor TACI, but the exact signaling mechanism was previously unclear.
- Research revealed that TACI's cytoplasmic domain binds to MyD88, an adaptor protein that activates NF-kappaB signaling, although TACI itself doesn’t have the traditional TIR domain found in similar receptors.
- The study showed that TACI triggers CSR through a MyD88-dependent pathway involving multiple signaling molecules, and that CSR is negatively affected in mice and humans lacking MyD88 or IRAK4, highlighting the unique role of MyD88 in B cell function.
Article Abstract
BAFF and APRIL are innate immune mediators that trigger immunoglobulin G (IgG) and IgA class-switch recombination (CSR) in B cells by engaging the receptor TACI. The mechanism that underlies CSR signaling by TACI remains unknown. Here we found that the cytoplasmic domain of TACI encompasses a conserved motif that bound MyD88, an adaptor that activates transcription factor NF-kappaB signaling pathways via a Toll-interleukin 1 (IL-1) receptor (TIR) domain. TACI lacks a TIR domain, yet triggered CSR via the DNA-editing enzyme AID by activating NF-kappaB through a Toll-like receptor (TLR)-like MyD88-IRAK1-IRAK4-TRAF6-TAK1 pathway. TACI-induced CSR was impaired in mice and humans lacking MyD88 or the kinase IRAK4, which indicates that MyD88 controls a B cell-intrinsic, TIR-independent, TACI-dependent pathway for immunoglobulin diversification.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3047500 | PMC |
| http://dx.doi.org/10.1038/ni.1914 | DOI Listing |
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