Research ArticleImmunology

Profiling the origin, dynamics, and function of traction force in B cell activation

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Sci. Signal.  07 Aug 2018:
Vol. 11, Issue 542, eaai9192
DOI: 10.1126/scisignal.aai9192

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B cells use the force

B cells recognize antigens through membrane-bound antibodies that are part of the B cell receptor (BCR). Antigen recognition stimulates BCR-dependent intracellular signaling that is required for B cell activation. Noting that B cells first spread over antigen-presenting surfaces before contracting, Wang et al. used traction force microscopy to measure the displacing forces exerted by B cells on fluorescent beads coated onto antigen-containing gel surfaces of different stiffness values. The authors found that memory B cells generated greater traction forces than did naïve B cells and that the strength of these forces was correlated with increased BCR microcluster mean fluorescent intensity. In addition, B cells from patients with rheumatoid arthritis exerted greater traction forces than did B cells from healthy donors, which may play a role in the enhanced activation of autoreactive B cells observed in these patients.

Abstract

B lymphocytes use B cell receptors (BCRs) to recognize membrane-bound antigens to further initiate cell spreading and contraction responses during B cell activation. We combined traction force microscopy and live-cell imaging to profile the origin, dynamics, and function of traction force generation in these responses. We showed that B cell activation required the generation of 10 to 20 nN of traction force when encountering antigens presented by substrates with stiffness values from 0.5 to 1 kPa, which mimic the rigidity of antigen-presenting cells in vivo. Perturbation experiments revealed that F-actin remodeling and myosin- and dynein-mediated contractility contributed to traction force generation and B cell activation. Moreover, membrane-proximal BCR signaling molecules (including Lyn, Syk, Btk, PLC-γ2, BLNK, and Vav3) and adaptor molecules (Grb2, Cbl, and Dok-3) linking BCR microclusters and motor proteins were also required for the sustained generation of these traction forces. We found a positive correlation between the strength of the traction force and the mean fluorescence intensity of the BCR microclusters. Furthermore, we demonstrated that isotype-switched memory B cells expressing immunoglobulin G (IgG)–BCRs generated greater traction forces than did mature naïve B cells expressing IgM-BCRs during B cell activation. Last, we observed that primary B cells from patients with rheumatoid arthritis generated greater traction forces than did B cells from healthy donors in response to antigen stimulation. Together, these data delineate the origin, dynamics, and function of traction force during B cell activation.

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