B cell receptor signaling in germinal centers prolongs survival and primes B cells for selection [bulk RNA-seq]

Germinal centers (GCs) are sites of B cell clonal expansion, diversification, and antibody affinity selection. This process is limited and directed by T follicular helper cells that provide helper signals to B cells that endocytose, process, and present cognate antigens in proportion to their B cell receptor (BCR) affinity. Under this model, the BCR functions as an endocytic receptor for antigen capture. How signaling through the BCR contributes to selection is not well understood. To investigate the role of BCR signaling in GC selection, we developed a tracker for antigen binding and presentation and a Bruton's tyrosine kinase drug-resistant-mutant mouse model. We showed that BCR signaling per se is necessary for the survival and priming of light zone B cells to receive T cell help. Our findings provide insight into how high-affinity antibodies are selected within GCs and are fundamental to our understanding of adaptive immunity and vaccine development. Overall design: GC B1-8 c-Myc-GFP cells were sorted based on Myc-GFP and NP-Ea fluorescence. mNnN: Myc Negative NP Negative mNnP: Myc Negative NP Positive mPnN: Myc Positive NP Negative mPnP: Myc Positive NP Positive