Arid1a-dependent canonical BAF complex suppresses inflammatory programs to drive efficient germinal center B cell...

Area of Science:

• Immunology
• Molecular Biology
• Cancer Biology

Background:

• Mammalian Brg1/Brm-associated factor (BAF) complexes regulate nucleosomal remodeling.
• BAF complexes are frequently mutated in cancers, including germinal center (GC)-derived B cell lymphomas.
• The specific roles of distinct BAF complexes in GC B cell biology remain unclear.

Purpose of the Study:

• To investigate the role of the AT-rich interaction domain 1a (Arid1a)-containing canonical BAF (cBAF) complex in GC B cell biology.
• To elucidate the mechanisms by which Arid1a influences GC maintenance and antibody responses.

Main Methods:

• Analysis of Arid1a-deficient B cells.
• Assessment of GC maintenance and antibody production.
• Investigation of chromatin landscapes and gene expression profiles.
• Evaluation of inflammatory cell recruitment and signaling pathways.

Main Results:

• Arid1a is required for sustained GC maintenance and high-affinity antibody responses.
• Arid1a-deficient B cells exhibit initial activation but fail to maintain the GC program.
• Arid1a establishes permissive chromatin for B cell activation and suppresses inflammatory gene programs.
• Arid1a deficiency leads to inflammatory signatures, recruiting neutrophils and monocytes.
• Interleukin-1β blockade or glucocorticoid receptor agonist partially rescued Arid1a-deficient GCs.

Conclusions:

• Arid1a-dependent cBAF complex plays essential roles in promoting efficient GC responses.
• Inflammation critically impedes GC function in the absence of Arid1a.
• Arid1a is crucial for balancing B cell activation and inflammatory responses within GCs.