Cited by 105T-cell and B-cell ImmunologyProtein Kinase Regulation and GTPase SignalingCellular transport and secretion

The Rap GTPases Regulate B Cell Morphology, Immune-Synapse Formation, and Signaling by Particulate B Cell Receptor Ligands

Open access
Lin, Kevin B.L., Freeman, Spencer A., Zabetian, Saba, Brugger, Hayley, Weber, Michele, Lei, Victor, Dang-Lawson, May, Tse, Kathy W.K. +3 more·2008·Immunity

Abstract

B lymphocytes spread and extend membrane processes when searching for antigens and form immune synapses upon contacting cells that display antigens on their surface. Although these dynamic morphological changes facilitate B cell activation, the signaling pathways underlying these processes are not fully understood. We found that activation of the Rap GTPases was essential for these changes in B cell morphology. Rap activation was important for B cell receptor (BCR)- and lymphocyte-function-associated antigen-1 (LFA-1)-induced spreading, for BCR-induced immune-synapse formation, and for particulate BCR ligands to induce localized F-actin assembly and membrane-process extension. Rap activation and F-actin assembly were also required for optimal BCR signaling in response to particulate antigens but not soluble antigens. Thus by controlling B cell morphology and cytoskeletal organization, Rap might play a key role in the activation of B cells by particulate and cell-associated antigens.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.immuni.2007.11.019

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Similar defects in B cell immune synapses likely underlie poor antibody responses after vaccination or infection in HEM1-deficient patients.

    “Similar defects in B cell immune synapses likely underlie poor antibody responses after vaccination or infection [9, 38].”

    From HEM1 Actin Immunodysregulatory Disorder: Genotypes, Phenotypes, and Future Directions (2022) · cites this paper as [38]

    The Results (page unavailable) show that blocking Rap activation impaired immune-synapse formation in experimental B cells. The paper does not study HEM1-deficient patients or establish that synapse defects underlie their poor antibody responses after vaccination or infection. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Part of this paper’s reference list could not be split into single entries.

Research works printed but not linked: 47

  1. [1]1. Allen, C.D. ∙ Okada, T. ∙ Tang, H.L. ... Imaging of germinal center selection events during affinity maturation Science. 2007; 315:528-531 Crossref Scopus (624) PubMed Google Scholar
  2. [2]2. Arthur, W.T. ∙ Quilliam, L.A. ∙ Cooper, J.A. Rap1 promotes cell spreading by localizing Rac guanine nucleotide exchange factors J. Cell Biol. 2004; 167:111-122 Crossref Scopus (221) PubMed Google Scholar
  3. [3]3. Badour, K. ∙ Zhang, J. ∙ Shi, F. ... Fyn and PTP-PEST-mediated regulation of Wiskott-Aldrich syndrome protein (WASp) tyrosine phosphorylation is required for coupling T cell antigen receptor engagement to WASp effector function and T cell activation J. Exp. Med. 2004; 199:99-112 Crossref Scopus (172) PubMed Google Scholar
  4. [4]4. Bajenoff, M. ∙ Egen, J.G. ∙ Koo, L.Y. ... Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes Immunity. 2006; 25:989-1001 Full Text Full Text (PDF) Scopus (790) PubMed Google Scholar
  5. [5]5. Batista, F.D. ∙ Iber, D. ∙ Neuberger, M.S. B cells acquire antigen from target cells after synapse formation Nature. 2001; 411:489-494 Crossref Scopus (514) PubMed Google Scholar
  6. [6]6. Bergtold, A. ∙ Desai, D.D. ∙ Gavhane, A. ... Cell surface recycling of internalized antigen permits dendritic cell priming of B cells Immunity. 2005; 23:503-514 Full Text Full Text (PDF) Scopus (324) PubMed Google Scholar
  7. [7]7. Bivona, T.G. ∙ Wiener, H.H. ∙ Ahearn, I.M. ... Rap1 up-regulation and activation on plasma membrane regulates T cell adhesion J. Cell Biol. 2004; 164:461-470 Crossref Scopus (146) PubMed Google Scholar
  8. [8]8. Boettner, B. ∙ Govek, E.E. ∙ Cross, J. ... The junctional multidomain protein AF-6 is a binding partner of the Rap1A GTPase and associates with the actin cytoskeletal regulator profilin Proc. Natl. Acad. Sci. USA. 2000; 97:9064-9069 Crossref Scopus (172) PubMed Google Scholar
  9. [9]9. Bos, J.L. Linking Rap to cell adhesion Curr. Opin. Cell Biol. 2005; 17:123-128 Crossref Scopus (408) PubMed Google Scholar
  10. [10]10. Carrasco, Y.R. ∙ Batista, F.D. B cell recognition of membrane-bound antigen: An exquisite way of sensing ligands Curr. Opin. Immunol. 2006; 18:286-291 Crossref Scopus (93) PubMed Google Scholar
  11. [11]11. Carrasco, Y.R. ∙ Batista, F.D. B-cell activation by membrane-bound antigens is facilitated by the interaction of VLA-4 with VCAM-1 EMBO J. 2006; 25:889-899 Crossref Scopus (126) PubMed Google Scholar
  12. [12]12. Carrasco, Y.R. ∙ Fleire, S.J. ∙ Cameron, T. ... LFA-1/ICAM-1 interaction lowers the threshold of B cell activation by facilitating B cell adhesion and synapse formation Immunity. 2004; 20:589-599 Full Text Full Text (PDF) Scopus (281) PubMed Google Scholar
  13. [13]13. Christian, S.L. ∙ Lee, R.L. ∙ McLeod, S.J. ... Activation of the Rap GTPases in B lymphocytes modulates B cell antigen receptor-induced activation of Akt but has no effect on MAP kinase activation J. Biol. Chem. 2003; 278:41756-41767 Full Text Full Text (PDF) Scopus (47) PubMed Google Scholar
  14. [14]14. Duchniewicz, M. ∙ Zemojtel, T. ∙ Kolanczyk, M. ... Rap1A-deficient T and B cells show impaired integrin-mediated cell adhesion Mol. Cell. Biol. 2006; 26:643-653 Crossref Scopus (102) PubMed Google Scholar
  15. [15]15. Durand, C.A. ∙ Westendorf, J. ∙ Tse, K.W. ... The Rap GTPases mediate CXCL13- and sphingosine 1-phosphate-induced chemotaxis, adhesion, and Pyk2 tyrosine phosphorylation in B lymphocytes Eur. J. Immunol. 2006; 36:2235-2249 Crossref Scopus (39) PubMed Google Scholar
  16. [16]16. Dustin, M.L. ∙ Cooper, J.A. The immunological synpase and the actin cytoskeleton: Molecular hardware for T cell signaling Nat. Immunol. 2000; 1:23-29 Crossref Scopus (572) PubMed Google Scholar
  17. [17]17. Fleire, S.J. ∙ Goldman, J.P. ∙ Carrasco, Y.R. ... B cell ligand discrimination through a spreading and contraction response Science. 2006; 312:738-741 Crossref Scopus (351) PubMed Google Scholar
  18. [18]18. Fu, Z. ∙ Lee, S.H. ∙ Simonetta, A. ... Differential roles of Rap1 and Rap2 small GTPases in neurite retraction and synapse elimination in hippocampal spiny neurons J. Neurochem. 2007; 100:118-131 Crossref Scopus (71) PubMed Google Scholar
  19. [19]19. Gerard, A. ∙ Mertens, A.E. ∙ van der Kammen, R.A. ... The Par polarity complex regulates Rap1- and chemokine-induced T cell polarization J. Cell Biol. 2007; 176:863-875 Crossref Scopus (105) PubMed Google Scholar
  20. [20]20. Gomez, T.S. ∙ Hamann, M.J. ∙ McCarney, S. ... Dynamin 2 regulates T cell activation by controlling actin polymerization at the immunological synapse Nat. Immunol. 2005; 6:261-270 Crossref Scopus (135) PubMed Google Scholar
  21. [21]21. Gomez, T.S. ∙ McCarney, S.D. ∙ Carrizosa, E. ... HS1 functions as an essential actin-regulatory adaptor protein at the immune synapse Immunity. 2006; 24:741-752 Full Text Full Text (PDF) Scopus (170) PubMed Google Scholar
  22. [22]22. Gupta, N. ∙ Wollscheid, B. ∙ Watts, J.D. ... Quantitative proteomic analysis of B cell lipid rafts reveals that ezrin regulates antigen receptor-mediated lipid raft dynamics Nat. Immunol. 2006; 7:625-633 Crossref Scopus (170) PubMed Google Scholar
  23. [23]23. Han, J. ∙ Lim, C.J. ∙ Watanabe, N. ... Reconstructing and deconstructing agonist-induced activation of integrin αIIbß3 Curr. Biol. 2006; 16:1796-1806 Full Text Full Text (PDF) Scopus (375) PubMed Google Scholar
  24. [24]24. Hauser, A.E. ∙ Junt, T. ∙ Mempel, T.R. ... Definition of germinal-center B cell migration in vivo reveals predominant intrazonal circulation patterns Immunity. 2007; 26:655-667 Full Text Full Text (PDF) Scopus (248) PubMed Google Scholar
  25. [25]25. Huang, N.N. ∙ Han, S.B. ∙ Hwang, I.Y. ... B cells productively engage soluble antigen-pulsed dendritic cells: Visualization of live-cell dynamics of B cell-dendritic cell interactions J. Immunol. 2005; 175:7125-7134 Crossref Scopus (46) PubMed Google Scholar
  26. [26]26. Jeon, T.J. ∙ Lee, D.J. ∙ Merlot, S. ... Rap1 controls cell adhesion and cell motility through the regulation of myosin II J. Cell Biol. 2007; 176:1021-1033 Crossref Scopus (95) PubMed Google Scholar
  27. [27]27. Kang, P.J. ∙ Sanson, A. ∙ Lee, B. ... A GDP/GTP exchange factor involved in linking a spatial landmark to cell polarity Science. 2001; 292:1376-1378 Crossref Scopus (85) PubMed Google Scholar
  28. [28]28. Katagiri, K. ∙ Imamura, M. ∙ Kinashi, T. Spatiotemporal regulation of the kinase Mst1 by binding protein RAPL is critical for lymphocyte polarity and adhesion Nat. Immunol. 2006; 7:919-928 Crossref Scopus (195) PubMed Google Scholar
  29. [29]29. Katagiri, K. ∙ Maeda, A. ∙ Shimonaka, M. ... RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1 Nat. Immunol. 2003; 4:741-748 Crossref Scopus (409) PubMed Google Scholar
  30. [30]30. Katagiri, K. ∙ Ohnishi, N. ∙ Kabashima, K. ... Crucial functions of the Rap1 effector molecule RAPL in lymphocyte and dendritic cell trafficking Nat. Immunol. 2004; 5:1045-1051 Crossref Scopus (165) PubMed Google Scholar
  31. [31]31. Kinashi, T. Intracellular signalling controlling integrin activation in lymphocytes Nat. Rev. Immunol. 2005; 5:546-559 Crossref Scopus (476) PubMed Google Scholar
  32. [32]32. Krummel, M.F. ∙ Macara, I. Maintenance and modulation of T cell polarity Nat. Immunol. 2006; 7:1143-1149 Crossref Scopus (150) PubMed Google Scholar
  33. [33]33. Lafuente, E.M. ∙ van Puijenbroek, A.A. ∙ Krause, M. ... RIAM, an Ena/VASP and Profilin ligand, interacts with Rap1-GTP and mediates Rap1-induced adhesion Dev. Cell. 2004; 7:585-595 Full Text Full Text (PDF) Scopus (332) PubMed Google Scholar
  34. [34]34. Lankar, D. ∙ Vincent-Schneider, H. ∙ Briken, V. ... Dynamics of major histocompatibility complex class II compartments during B cell receptor-mediated cell activation J. Exp. Med. 2002; 195:461-472 Crossref Scopus (106) PubMed Google Scholar
  35. [35]35. Ludford-Menting, M.J. ∙ Oliaro, J. ∙ Sacirbegovic, F. ... A network of PDZ-containing proteins regulates T cell polarity and morphology during migration and immunological synapse formation Immunity. 2005; 22:737-748 Full Text Full Text (PDF) Scopus (218) PubMed Google Scholar
  36. [36]36. McLeod, S.J. ∙ Li, A.H. ∙ Lee, R.L. ... The Rap GTPases regulate B cell migration toward the chemokine stromal cell-derived factor-1 (CXCL12): Potential role for Rap2 in promoting B cell migration J. Immunol. 2002; 169:1365-1371 Crossref Scopus (99) PubMed Google Scholar
  37. [37]37. McLeod, S.J. ∙ Shum, A.J. ∙ Lee, R.L. ... The Rap GTPases regulate integrin-mediated adhesion, cell spreading, actin polymerization, and Pyk2 tyrosine phosphorylation in B lymphocytes J. Biol. Chem. 2004; 279:12009-12019 Full Text Full Text (PDF) Scopus (121) PubMed Google Scholar
  38. [38]38. Miertzschke, M. ∙ Stanley, P. ∙ Bunney, T.D. ... Characterisation of interactions of adaptor protein RAPL/Nore1 with Rap GTPases and their role in T cell migration J. Biol. Chem. 2007; 282:30629-30642 Full Text Full Text (PDF) Scopus (34) PubMed Google Scholar
  39. [39]39. Mochizuki, N. ∙ Ohba, Y. ∙ Kiyokawa, E. ... Activation of the ERK/MAPK pathway by an isoform of rap1GAP associated with G alpha(i) Nature. 1999; 400:891-894 Crossref Scopus (196) PubMed Google Scholar
  40. [40]40. Ohba, Y. ∙ Mochizuki, N. ∙ Matsuo, K. ... Rap2 as a slowly responding molecular switch in the Rap1 signaling cascade Mol. Cell. Biol. 2000; 20:6074-6083 Crossref Scopus (96) PubMed Google Scholar
  41. [41]41. Paavilainen, V.O. ∙ Bertling, E. ∙ Falck, S. ... Regulation of cytoskeletal dynamics by actin-monomer-binding proteins Trends Cell Biol. 2004; 14:386-394 Full Text Full Text (PDF) Scopus (202) PubMed Google Scholar
  42. [42]42. Polakis, P.G. ∙ Rubinfeld, B. ∙ Evans, T. ... Purification of a plasma membrane-associated GTPase-activating protein specific for rap1/Krev-1 from HL60 cells Proc. Natl. Acad. Sci. USA. 1991; 88:239-243 Crossref Scopus (84) PubMed Google Scholar
  43. [43]43. Qi, H. ∙ Egen, J.G. ∙ Huang, A.Y. ... Extrafollicular activation of lymph node B cells by antigen-bearing dendritic cells Science. 2006; 312:1672-1676 Crossref Scopus (434) PubMed Google Scholar
  44. [44]44. Reedquist, K.A. ∙ Ross, E. ∙ Koop, E.A. ... The small GTPase, Rap1, mediates CD31-induced integrin adhesion J. Cell Biol. 2000; 148:1151-1158 Crossref Scopus (367) PubMed Google Scholar
  45. [45]45. Shimonaka, M. ∙ Katagiri, K. ∙ Nakayama, T. ... Rap1 translates chemokine signals to integrin activation, cell polarization, and motility across vascular endothelium under flow J. Cell Biol. 2003; 161:417-427 Crossref Scopus (317) PubMed Google Scholar
  46. [46]46. Stork, P.J. ∙ Dillon, T.J. Multiple roles of Rap1 in hematopoietic cells: Complementary versus antagonistic functions Blood. 2005; 106:2952-2961 Crossref Scopus (93) PubMed Google Scholar
  47. [47]47. Suga, K. ∙ Katagiri, K. ∙ Kinashi, T. ... CD98 induces LFA-1-mediated cell adhesion in lymphoid cells via activation of Rap1 FEBS Lett. 2001; 489:249-253 Crossref Scopus (60) PubMed Google Scholar

Cited by

Sorted by citations

Authors
Lin, K. B. L., Freeman, S. A., Zabetian, S., Brugger, H., Weber, M., Lei, V., Dang-Lawson, M., Tse, K. W. K., Santamaria, R., Batista, F. D., & Gold, M. R.
Affiliations
  • University of British Columbia (CA)
  • Cancer Research UK (GB)
Corresponding author
Gold, Michael R.
Venue
Immunity
Publisher
Elsevier BV
Published
2008-01
Volume
28
Issue
1
Pages
75-87
ISSN
1074-7613 (ISSN-L)
OpenAlex
W2086285294
Cited by
105
References
0
Citations by year
2025: 4 · 2024: 1 · 2023: 1 · 2022: 4 · 2021: 1 · 2020: 4 · 2019: 5 · 2018: 10 · 2017: 5 · 2016: 2 · 2015: 7 · 2014: 3 · 2013: 6 · 2012: 5
FWCI
6.17
Type
journal article
Language
en
Open access
Locations
  • Immunity (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Michael Smith Health Research BC
  • Canadian Institutes of Health Research
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
Rap GTPases, immune synapse formation, B cell receptor signaling, particulate antigen, LFA-1, F-actin assembly, cytoskeleton, B cell activation
MeSH terms
Actins, Animals, B-Lymphocytes, Cell Line, Enzyme Activation, Humans, Lymphocyte Activation, Microscopy, Electron, Scanning, Receptors, Antigen, B-Cell, Signal Transduction, Antigen Presentation, Microscopy, Confocal, rap GTP-Binding Proteins, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review