B cell receptor signaling in germinal centers prolongs survival and primes B cells for selection

被引:40
|
作者
Chen, Spencer T. [1 ]
Oliveira, Thiago Y. [1 ]
Gazumyan, Anna [1 ]
Cipolla, Melissa [1 ]
Nussenzweig, Michel C. [1 ,2 ]
机构
[1] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA
[2] Rockefeller Univ, Howard Hughes Med Inst HHMI, New York, NY 10065 USA
关键词
MEMORY B; TRANSCRIPTION FACTOR; C-MYC; AFFINITY MATURATION; SOLUBLE-ANTIGEN; GENE-EXPRESSION; DENDRITIC CELLS; PLASMA-CELL; RNA-SEQ; DIFFERENTIATION;
D O I
10.1016/j.immuni.2023.02.003
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 en-docytose, 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.
引用
收藏
页码:547 / +
页数:23
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