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Excel · study · 2026

RAG1-Independent Atypical B Cell Development in Chickens: Redefining the Role of RAG1 in Avian Immunology

Listed in NCBI GEO

The importance of RAG1 in avian B cell development has been a topic of significant debate, as chickens exhibit limited antibody diversity through RAG1-mediated V(D)J recombination compared to mammals.

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In chickens, antibody diversity is predominantly achieved through gene conversion in the bursa of Fabricius. However, the absence of RAG1 disrupts gene conversion and impairs B cell signaling pathways, underscoring its importance.

In this study, we utilized a RAG1-deficient chicken model to uncover a classical RAG1-dependent and an alternative RAG1-independent B cell developmental pathway unique to avians. Unlike mammals, where RAG1-induced double-strand breaks (DSBs) activate ATM-dependent DNA damage responses (DDR) for B cell development, we found that ATR mediates this process in chickens. In RAG1-deficient chicken bursa, normal development of B cells is halted due to the absence of V(D)J recombination and reduced ATR-mediated B cell development signals.

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Although the absence of RAG1 significantly reduced B cell numbers, a small number of B cell subset was still observed. These atypical B cells (ABCs), which developed in the bursa, exhibited reduced ATR-mediated signaling but elevated expression of inflammatory and migration-related genes, allowing them to migrate into the bursa. ABCs were also specifically observed in peripheral organ (spleen) of RAG1-deficient chicken and expressed IgM with only harboring J and C segments.

Additionally, ABCs displayed autoimmune-like phenotypes, including lysosome, TLR signaling activation, autophagy, and inflammation. This study highlights avian-specific alternative RAG1-independent B cell development and provides insights into autoantibody-independent mechanisms of autoimmune diseases, contributing to comparative immunology and therapeutic development.

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Life Sciences
Provenance · 1 source records, 7 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE29365714 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[organism].NCBITaxon:9031source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title