title: The activation of IgM- or isotype-switched IgG- and IgE-BCR exhibits distinct mechanical force sensitivity and threshold.
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.
authors.affiliation: MOE Key Laboratory of Protein Sciences, Tsinghua University, Beijing, China.
authors.forename: Zhengpeng
authors.initials: Z
authors.lastname: Wan
authors.affiliation: MOE Key Laboratory of Protein Sciences, Tsinghua University, Beijing, China.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Chen
authors.affiliation: Natural Products Research Center, Chengdu Institution of Biology, Chinese Academy of Science, Chengdu, China.
authors.forename: Haodong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Ji
authors.affiliation: MOE Key Laboratory of Protein Sciences, Tsinghua University, Beijing, China.
authors.forename: Yingjia
authors.initials: Y
authors.lastname: Chen
authors.affiliation: MOE Key Laboratory of Protein Sciences, Tsinghua University, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: MOE Key Laboratory of Protein Sciences, Tsinghua University, Beijing, China.
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Natural Products Research Center, Chengdu Institution of Biology, Chinese Academy of Science, Chengdu, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Jizhong
authors.initials: J
authors.lastname: Lou
authors.affiliation: Natural Products Research Center, Chengdu Institution of Biology, Chinese Academy of Science, Chengdu, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Tang
authors.affiliation: MOE Key Laboratory of Protein Sciences, Tsinghua University, Beijing, China.
authors.forename: Wanli
authors.initials: W
authors.lastname: Liu
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism*; D002460:Cell Line; D055598:Chemical Phenomena; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism*; D007075:Immunoglobulin M / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*
chemical_list: D000941:Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D007073:Immunoglobulin E
keywords: BCR activation; IgG-BCR; IgM-BCR; TGT; human; immunology; mechanical force; mouse