The Activation of IgM- or Isotype-switched IgG- and IgE-BCR Exhibits Distinct Mechanical Force Sensitivity and Threshold

Overview

Journal Elife

Specialty Biology

Date 2015 Aug 11

PMID 26258882

Citations 54

Authors

Zhengpeng Wan

Xiangjun Chen

Haodong Chen

Qinghua Ji

Yingjia Chen

Jing Wang

Yiyun Cao

Fei Wang

Jizhong Lou

Zhuo Tang

Wanli Liu

Affiliations

Soon will be listed here.

Abstract

B lymphocytes use B cell receptors (BCRs) to sense the physical features of the antigens. However, the sensitivity and threshold for the activation of BCRs resulting from the stimulation by mechanical forces are unknown. Here, we addressed this question using a double-stranded DNA-based tension gauge tether system serving as a predefined mechanical force gauge ranging from 12 to 56 pN. We observed that IgM-BCR activation is dependent on mechanical forces and exhibits a multi-threshold effect. In contrast, the activation of isotype-switched IgG- or IgE-BCR only requires a low threshold of less than 12 pN, providing an explanation for their rapid activation in response to antigen stimulation. Mechanistically, we found that the cytoplasmic tail of the IgG-BCR heavy chain is both required and sufficient to account for the low mechanical force threshold. These results defined the mechanical force sensitivity and threshold that are required to activate different isotyped BCRs.

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