The Membrane Skeleton Controls Diffusion Dynamics and Signaling Through the B Cell Receptor

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2010 Feb 23

PMID 20171124

Citations 163

Authors

Bebhinn Treanor

David Depoil

Aitor Gonzalez-Granja

Patricia Barral

Michele Weber

Omer Dushek

Andreas Bruckbauer

Facundo D Batista

Affiliations

Soon will be listed here.

Abstract

Early events of B cell activation after B cell receptor (BCR) triggering have been well characterized. However, little is known about the steady state of the BCR on the cell surface. Here, we simultaneously visualize single BCR particles and components of the membrane skeleton. We show that an ezrin- and actin-defined network influenced steady-state BCR diffusion by creating boundaries that restrict BCR diffusion. We identified the intracellular domain of Igbeta as important in mediating this restriction in diffusion. Importantly, alteration of this network was sufficient to induce robust intracellular signaling and concomitant increase in BCR mobility. Moreover, by using B cells deficient in key signaling molecules, we show that this signaling was most probably initiated by the BCR. Thus, our results suggest the membrane skeleton plays a crucial function in controlling BCR dynamics and thereby signaling, in a way that could be important for understanding tonic signaling necessary for B cell development and survival.

Citing Articles

A programmable biomimetic cytoskeleton.

Niederholtmeyer H Nat Chem. 2025; 17(3):311-313.

PMID: 39994490 DOI: 10.1038/s41557-025-01757-4.

Towards a unifying model for B-cell receptor triggering.

Degn S, Tolar P Nat Rev Immunol. 2024; 25(2):77-91.

PMID: 39256626 DOI: 10.1038/s41577-024-01073-x.

Podosome Nucleation Is Facilitated by Multivalent Interactions between Syk and ITAM-containing Membrane Complexes.

Ghasempour S, Muise A, Freeman S J Immunol. 2024; 213(7):988-997.

PMID: 39140892 PMC: 11404668. DOI: 10.4049/jimmunol.2400031.

Hem1 inborn errors of immunity: waving goodbye to coordinated immunity in mice and humans.

Christodoulou A, Tsai J, Suwankitwat N, Anderson A, Iritani B Front Immunol. 2024; 15:1402139.

PMID: 39026677 PMC: 11254771. DOI: 10.3389/fimmu.2024.1402139.

Mechanical regulation of lymphocyte activation and function.

Pathni A, Wagh K, Rey-Suarez I, Upadhyaya A J Cell Sci. 2024; 137(13).

PMID: 38995113 PMC: 11267459. DOI: 10.1242/jcs.219030.

References

Williams G, Peaker C, Patel K, Neuberger M . The alpha/beta sheath and its cytoplasmic tyrosines are required for signaling by the B-cell antigen receptor but not for capping or for serine/threonine-kinase recruitment. Proc Natl Acad Sci U S A. 1994; 91(2):474-8. PMC: 42971. DOI: 10.1073/pnas.91.2.474. View

Lillemeier B, Pfeiffer J, Surviladze Z, Wilson B, Davis M . Plasma membrane-associated proteins are clustered into islands attached to the cytoskeleton. Proc Natl Acad Sci U S A. 2006; 103(50):18992-7. PMC: 1681352. DOI: 10.1073/pnas.0609009103. View

Lenne P, Wawrezinieck L, Conchonaud F, Wurtz O, Boned A, Guo X . Dynamic molecular confinement in the plasma membrane by microdomains and the cytoskeleton meshwork. EMBO J. 2006; 25(14):3245-56. PMC: 1523176. DOI: 10.1038/sj.emboj.7601214. View

Lam K, Kuhn R, Rajewsky K . In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid cell death. Cell. 1997; 90(6):1073-83. DOI: 10.1016/s0092-8674(00)80373-6. View

Wienands J, Reth M . Glycosyl-phosphatidylinositol linkage as a mechanism for cell-surface expression of immunoglobulin D. Nature. 1992; 356(6366):246-8. DOI: 10.1038/356246a0. View

Vrljic M, Nishimura S, Moerner W, McConnell H . Cholesterol depletion suppresses the translational diffusion of class II major histocompatibility complex proteins in the plasma membrane. Biophys J. 2004; 88(1):334-47. PMC: 1305010. DOI: 10.1529/biophysj.104.045989. View

Dix J, Verkman A . Crowding effects on diffusion in solutions and cells. Annu Rev Biophys. 2008; 37:247-63. DOI: 10.1146/annurev.biophys.37.032807.125824. View

Tang Q, Edidin M . Lowering the barriers to random walks on the cell surface. Biophys J. 2003; 84(1):400-7. PMC: 1302621. DOI: 10.1016/S0006-3495(03)74860-7. View

Lin K, Freeman S, Zabetian S, Brugger H, Weber M, Lei V . The rap GTPases regulate B cell morphology, immune-synapse formation, and signaling by particulate B cell receptor ligands. Immunity. 2008; 28(1):75-87. DOI: 10.1016/j.immuni.2007.11.019. View

10.

Wade W, Freed J, Edidin M . Translational diffusion of class II major histocompatibility complex molecules is constrained by their cytoplasmic domains. J Cell Biol. 1989; 109(6 Pt 2):3325-31. PMC: 2115898. DOI: 10.1083/jcb.109.6.3325. View

11.

Haggie P, Kim J, Lukacs G, Verkman A . Tracking of quantum dot-labeled CFTR shows near immobilization by C-terminal PDZ interactions. Mol Biol Cell. 2006; 17(12):4937-45. PMC: 1679663. DOI: 10.1091/mbc.e06-08-0670. View

12.

Aitken C, Marshall R, Puglisi J . An oxygen scavenging system for improvement of dye stability in single-molecule fluorescence experiments. Biophys J. 2007; 94(5):1826-35. PMC: 2242739. DOI: 10.1529/biophysj.107.117689. View

13.

Tolar P, Sohn H, Pierce S . The initiation of antigen-induced B cell antigen receptor signaling viewed in living cells by fluorescence resonance energy transfer. Nat Immunol. 2005; 6(11):1168-76. DOI: 10.1038/ni1262. View

14.

Bretscher A, Edwards K, Fehon R . ERM proteins and merlin: integrators at the cell cortex. Nat Rev Mol Cell Biol. 2002; 3(8):586-99. DOI: 10.1038/nrm882. View

15.

DeFranco A . The complexity of signaling pathways activated by the BCR. Curr Opin Immunol. 1997; 9(3):296-308. DOI: 10.1016/s0952-7915(97)80074-x. View

16.

Faure S, Salazar-Fontana L, Semichon M, Tybulewicz V, Bismuth G, Trautmann A . ERM proteins regulate cytoskeleton relaxation promoting T cell-APC conjugation. Nat Immunol. 2004; 5(3):272-9. DOI: 10.1038/ni1039. View

17.

Weber M, Treanor B, Depoil D, Shinohara H, Harwood N, Hikida M . Phospholipase C-gamma2 and Vav cooperate within signaling microclusters to propagate B cell spreading in response to membrane-bound antigen. J Exp Med. 2008; 205(4):853-68. PMC: 2292224. DOI: 10.1084/jem.20072619. View

18.

Kusumi A, Sako Y, Yamamoto M . Confined lateral diffusion of membrane receptors as studied by single particle tracking (nanovid microscopy). Effects of calcium-induced differentiation in cultured epithelial cells. Biophys J. 1993; 65(5):2021-40. PMC: 1225938. DOI: 10.1016/S0006-3495(93)81253-0. View

19.

Goodnow C, Crosbie J, Adelstein S, Lavoie T, Brink R, Wotherspoon J . Altered immunoglobulin expression and functional silencing of self-reactive B lymphocytes in transgenic mice. Nature. 1988; 334(6184):676-82. DOI: 10.1038/334676a0. View

20.

Batista F, Harwood N . The who, how and where of antigen presentation to B cells. Nat Rev Immunol. 2008; 9(1):15-27. DOI: 10.1038/nri2454. View