A Germinal Center Checkpoint of AIRE in B Cells LimitsAntibody Diversification
Zhou, J. Z.; Huang, B.; Pei, B.; Sun, G.; Pawlitz, M.; ZHANG, W.; Li, x.; Hokynar, K. C.; Yao, F.; Perera, M. L.; Wei, S.; Zheng, S.; Polin, L. A.; Poulik, J. M.; Ranki, A.; Krohn, K.; Cunningham-Rundles, C.; Yang, N.; Bhagwat, A.; Yu, K.; Peterson, P.; Kisand, K.; Vuong, B. Q.; Cerutti, A.; Chen, K.
Show abstract
In response to antigens, B cells undergo affinity maturation and class switching mediated by activation-induced cytidine deaminase (AID) in germinal centers (GCs) of secondary lymphoid organs, but uncontrolled AID activity can precipitate autoimmunity and cancer. The regulation of GC antibody diversification is of fundamental importance but not well understood. We found that autoimmune regulator (AIRE), the molecule essential for T cell tolerance, is expressed in GC B cells in a CD40-dependent manner, interacts with AID and negatively regulates antibody affinity maturation and class switching by inhibiting AID function. AIRE deficiency in B cells caused altered antibody repertoire, increased somatic hypermutations, elevated autoantibodies to T helper 17 effector cytokines and defective control of skin Candida albicans. These results define a GC B cell checkpoint of humoral immunity and illuminate new approaches of generating high-affinity neutralizing antibodies for immunotherapy.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- B Cell Division Capacity in Germinal Centers Depends on Myc Transcript Stabilization Through m6A mRNA Methylation and IGF2BP3 Functions 97%
- Cyclin D3 drives inertial cell cycling in dark zone germinal center B cells 97%
- IRF7 controls spontaneous autoimmune germinal center and plasma cell checkpoints 96%
Similar papers in this journal
- The Structure-Selective Endonucleases GEN1 and MUS81 are Functionally Complementary in Safeguarding the Genome of Proliferating B Lymphocytes 97%
- Protein kinase Cδ is essential for the IgG response against T cell-independent type 2 antigens and commensal bacteria 97%
- Kidins220 regulates the development of B cells bearing the {lambda} light chain 96%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.