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Sci Rep. 2017 Nov 2;7(1):14888. doi: 10.1038/s41598-017-13993-x.

A model integrating tonic and antigen-triggered BCR signals to predict the survival of primary B cells.

Author information

1
Department of Computational Intelligence and Systems Science, Tokyo Institute of Technology, Yokohama 226-8502, Japan.
2
Department of Integrative Medicine and Neurobiology, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
3
School of Computing, Tokyo Institute of Technology, Yokohama 226-8502, Japan. my@c.titech.ac.jp.
4
Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. wang@fudan.edu.cn.

Abstract

The BCR constitutively transmits a "tonic" survival signal in the absence of exogenous antigen-binding. However, the strength of tonic BCR signal and its relationship with antigen-triggered survival signal are poorly understood. We found that primary B cells expressing high levels of BCR had elevated BCR tonic signal and increased survival compared with those expressing low levels of BCR. In addition, we found that crosslinking BCR with low doses of F(ab')2 α-IgM antibodies did not enhance, but rather decreased, B cell survival and that only when most of the BCR were occupied by F(ab')2 α-IgM antibodies was B cell survival enhanced. Based on these experimental results, we present a mathematical model integrating tonic and antigen-triggered BCR signals. Our model indicates that the signal generated from crosslinked BCR is 4.3 times as strong as the tonic signal generated from free BCR and that the threshold of B cell activation corresponds to the signal generated by crosslinking 61% of the surface BCR. This model also allows the prediction of the survival probability of a B cell based on its initial BCR level and the strength and duration of antigen stimulation, and fits with the mechanism of B cell tolerance.

PMID:
29097663
PMCID:
PMC5668375
DOI:
10.1038/s41598-017-13993-x
[Indexed for MEDLINE]
Free PMC Article

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