EndoU is a novel regulator of AICD during peripheral B cell selection.
Balanced transmembrane signals maintain a competent peripheral B cell pool limited in self-reactive B cells that may produce pathogenic autoantibodies. To identify molecules regulating peripheral B cell survival and tolerance to self-antigens (Ags), a gene modifier screen was performed with B cells from CD22-deficient C57BL/6 (CD22(-/-[B6])) mice that undergo activation-induced cell death (AICD) and fail to up-regulate c-Myc expression after B cell Ag receptor ligation. Likewise, lysozyme auto-Ag-specific B cells in Ig(Tg) hen egg lysozyme (HEL) transgenic mice inhabit the spleen but undergo AICD after auto-Ag encounter. This gene modifier screen identified EndoU, a single-stranded RNA-binding protein of ancient origin, as a major regulator of B cell survival in both models. EndoU gene disruption prevents AICD and normalizes c-Myc expression. These findings reveal that EndoU is a critical regulator of an unexpected and novel RNA-dependent pathway controlling peripheral B cell survival and Ag responsiveness that may contribute to peripheral B cell tolerance.
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Related Subject Headings
- Uridylate-Specific Endoribonucleases
- Signal Transduction
- Sialic Acid Binding Ig-like Lectin 2
- Self Tolerance
- Quantitative Trait Loci
- Proto-Oncogene Proteins c-myc
- Mice, Knockout
- Mice, Inbred C57BL
- Mice
- Immunology
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Uridylate-Specific Endoribonucleases
- Signal Transduction
- Sialic Acid Binding Ig-like Lectin 2
- Self Tolerance
- Quantitative Trait Loci
- Proto-Oncogene Proteins c-myc
- Mice, Knockout
- Mice, Inbred C57BL
- Mice
- Immunology