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Germinal Center Dynamics Revealed by Multiphoton Microscopy with a Photoactivatable Fluorescent Reporter

Victora, Gabriel D., Schwickert, Tanja A., Fooksman, David R., Kamphorst, Alice O., Meyer-Hermann, Michael, Dustin, Michael L., Nussenzweig, Michel C.·2010·Cell

Abstract

SUMMARY The germinal center (GC) reaction produces high-affinity antibodies by random mutation and selective clonal expansion of B cells with high-affinity receptors. However, the mechanism by which B cells are selected remains unclear, as does the role of the two anatomically-defined areas of the GC, light zone (LZ) and dark zone (DZ). We combined a new transgenic photoactivatable green fluorescent protein (PA-GFP) tracer with multiphoton laser-scanning microscopy and flow cytometry to examine anatomically defined LZ and DZ B cells and GC selection. We find that B cell division is restricted to the DZ, and that there is a net vector of B cell movement from the DZ to the LZ. The decision to return from the LZ to the DZ and undergo clonal expansion is controlled by T cells, which discern between LZ B cells based on the amount of antigen captured, providing a mechanism for GC selection.

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Research works printed but not linked: 71

  1. Allen, 2004, Germinal center dark and light zone organization is mediated by CXCR4 and CXCR5, Nat. Immunol., 5, 943, 10.1038/ni1100 · DOI · Paper page
  2. Allen, 2007, Germinal-center organization and cellular dynamics, Immunity, 27, 190, 10.1016/j.immuni.2007.07.009 · DOI · Paper page
  3. Allen, 2007, Imaging of germinal center selection events during affinity maturation, Science, 315, 528, 10.1126/science.1136736 · DOI
  4. Allen, 1988, Antibody engineering for the analysis of affinity maturation of an anti-hapten response, EMBO J., 7, 1995, 10.1002/j.1460-2075.1988.tb03038.x · DOI · Paper page
  5. Basso, 2004, Tracking CD40 signaling during germinal center development, Blood, 104, 4088, 10.1182/blood-2003-12-4291 · DOI
  6. Batista, 2001, B cells acquire antigen from target cells after synapse formation, Nature, 411, 489, 10.1038/35078099 · DOI
  7. Boscardin, 2006, Antigen targeting to dendritic cells elicits long-lived T cell help for antibody responses, J. Exp. Med., 203, 599, 10.1084/jem.20051639 · DOI · Paper page
  8. Brink, 2008, Visualizing the effects of antigen affinity on T-dependent B-cell differentiation, Immunol. Cell Biol., 86, 31, 10.1038/sj.icb.7100143 · DOI
  9. Corish, 1999, Attenuation of green fluorescent protein half-life in mammalian cells, Protein Eng., 12, 1035, 10.1093/protein/12.12.1035 · DOI · Paper page
  10. Delbos, 2005, Contribution of DNA polymerase eta to immunoglobulin gene hypermutation in the mouse, J. Exp. Med., 201, 1191, 10.1084/jem.20050292 · DOI
  11. Depoil, 2005, Immunological synapses are versatile structures enabling selective T cell polarization, Immunity, 22, 185, 10.1016/j.immuni.2004.12.010 · DOI
  12. Eisen, 1964, Variations in affinities of antibodies during the immune response, Biochemistry, 3, 996, 10.1021/bi00895a027 · DOI · Paper page
  13. Figge, 2008, Deriving a germinal center lymphocyte migration model from two-photon data, J. Exp. Med., 205, 3019, 10.1084/jem.20081160 · DOI
  14. Fooksman, 2010, Development and migration of plasma cells in the mouse lymph node, Immunity, 33, 118, 10.1016/j.immuni.2010.06.015 · DOI
  15. Germain, 2006, Dynamic imaging of the immune system: progress, pitfalls and promise, Nat. Rev. Immunol., 6, 497, 10.1038/nri1884 · DOI · Paper page
  16. Goidl, 1968, The effect of antigen dose and time after immunization on the amount and affinity of anti-hapten antibody, J. Immunol., 100, 371, 10.4049/jimmunol.100.2.371 · DOI
  17. Guo, 2000, A monoclonal antibody to the DEC-205 endocytosis receptor on human dendritic cells, Hum. Immunol., 61, 729, 10.1016/S0198-8859(00)00144-0 · DOI
  18. Han, 1995, Cellular interaction in germinal centers. Roles of CD40 ligand and B7-2 in established germinal centers, J. Immunol., 155, 556, 10.4049/jimmunol.155.2.556 · DOI · Paper page
  19. Han, 1995, In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. IV. Affinity-dependent, antigen-driven B cell apoptosis in germinal centers as a mechanism for maintaining self-tolerance, J. Exp. Med., 182, 1635, 10.1084/jem.182.6.1635 · DOI
  20. Hauser, 2007, Definition of germinal-center B cell migration in vivo reveals predominant intrazonal circulation patterns, Immunity, 26, 655, 10.1016/j.immuni.2007.04.008 · DOI
  21. Hauser, 2007, In vivo imaging studies shed light on germinal-centre development, Nat. Rev. Immunol., 7, 499, 10.1038/nri2120 · DOI
  22. Högerkorp, 2006, The human CD77- B cell population represents a heterogeneous subset of cells comprising centroblasts, centrocytes, and plasmablasts, prompting phenotypical revision, J. Immunol., 177, 4341, 10.4049/jimmunol.177.7.4341 · DOI
  23. Huntington, 2006, CD45 links the B cell receptor with cell survival and is required for the persistence of germinal centers, Nat. Immunol., 7, 190, 10.1038/ni1292 · DOI
  24. Jiang, 1995, The receptor DEC-205 expressed by dendritic cells and thymic epithelial cells is involved in antigen processing, Nature, 375, 151, 10.1038/375151a0 · DOI · Paper page
  25. Kamphorst, 2010, Route of antigen uptake differentially impacts presentation by dendritic cells and activated monocytes, J. Immunol., 185, 3426, 10.4049/jimmunol.1001205 · DOI
  26. Katz, 1970, Carrier function in anti-hapten immune responses. I. Enhancement of primary and secondary anti-hapten antibody responses by carrier preimmunization, J. Exp. Med., 132, 261, 10.1084/jem.132.2.261 · DOI
  27. Kim, 2010, Inhibition of follicular T-helper cells by CD8(+) regulatory T cells is essential for self tolerance, Nature, 467, 328, 10.1038/nature09370 · DOI
  28. Klein, 2008, Germinal centres: role in B-cell physiology and malignancy, Nat. Rev. Immunol., 8, 22, 10.1038/nri2217 · DOI
  29. Lanzavecchia, 1985, Antigen-specific interaction between T and B cells, Nature, 314, 537, 10.1038/314537a0 · DOI · Paper page
  30. Liu, 1989, Mechanism of antigen-driven selection in germinal centres, Nature, 342, 929, 10.1038/342929a0 · DOI · Paper page
  31. Liu, 1991, Sites of specific B cell activation in primary and secondary responses to T cell-dependent and T cell-independent antigens, Eur. J. Immunol., 21, 2951, 10.1002/eji.1830211209 · DOI
  32. MacLennan, 1994, Germinal centers, Annu. Rev. Immunol., 12, 117, 10.1146/annurev.iy.12.040194.001001 · DOI · Paper page
  33. Manser, 2004, Textbook germinal centers?, J. Immunol., 172, 3369, 10.4049/jimmunol.172.6.3369 · DOI
  34. McKean, 1984, Generation of antibody diversity in the immune response of BALB/c mice to influenza virus hemagglutinin, Proc. Natl. Acad. Sci. USA, 81, 3180, 10.1073/pnas.81.10.3180 · DOI
  35. Meyer-Hermann, 2001, Recycling probability and dynamical properties of germinal center reactions, J. Theor. Biol., 210, 265, 10.1006/jtbi.2001.2297 · DOI
  36. Meyer-Hermann, 2009, Germinal centres seen through the mathematical eye: B-cell models on the catwalk, Trends Immunol., 30, 157, 10.1016/j.it.2009.01.005 · DOI
  37. Meyer-Hermann, 2006, An analysis of B cell selection mechanisms in germinal centers, Math. Med. Biol., 23, 255, 10.1093/imammb/dql012 · DOI
  38. Nagaoka, 2000, Immunization and infection change the number of recombination activating gene (RAG)-expressing B cells in the periphery by altering immature lymphocyte production, J. Exp. Med., 191, 2113, 10.1084/jem.191.12.2113 · DOI
  39. Nie, 2004, The role of CXCR4 in maintaining peripheral B cell compartments and humoral immunity, J. Exp. Med., 200, 1145, 10.1084/jem.20041185 · DOI
  40. Nieuwenhuis, 1984, Functional anatomy of germinal centers, Am. J. Anat., 170, 421, 10.1002/aja.1001700315 · DOI
  41. Nowotschin, 2009, Use of KikGR a photoconvertible green-to-red fluorescent protein for cell labeling and lineage analysis in ES cells and mouse embryos, BMC Dev. Biol., 9, 49, 10.1186/1471-213X-9-49 · DOI
  42. Nussenzweig, 1967, Antihapten antibody specificity and L chain type, J. Exp. Med., 126, 727, 10.1084/jem.126.4.727 · DOI
  43. Oprea, 1997, Somatic mutation leads to efficient affinity maturation when centrocytes recycle back to centroblasts, J. Immunol., 158, 5155, 10.4049/jimmunol.158.11.5155 · DOI
  44. Patterson, 2002, A photoactivatable GFP for selective photolabeling of proteins and cells, Science, 297, 1873, 10.1126/science.1074952 · DOI · Paper page
  45. Paus, 2006, Antigen recognition strength regulates the choice between extrafollicular plasma cell and germinal center B cell differentiation, J. Exp. Med., 203, 1081, 10.1084/jem.20060087 · DOI · Paper page
  46. Phan, 2006, High affinity germinal center B cells are actively selected into the plasma cell compartment, J. Exp. Med., 203, 2419, 10.1084/jem.20061254 · DOI
  47. Pulendran, 1995, Soluble antigen can cause enhanced apoptosis of germinal-centre B cells, Nature, 375, 331, 10.1038/375331a0 · DOI
  48. Rajewsky, 1996, Clonal selection and learning in the antibody system, Nature, 381, 751, 10.1038/381751a0 · DOI
  49. Rajewsky, 1969, The requirement of more than one antigenic determinant for immunogenicity, J. Exp. Med., 129, 1131, 10.1084/jem.129.6.1131 · DOI · Paper page
  50. Rock, 1984, Antigen presentation by hapten-specific B lymphocytes. I. Role of surface immunoglobulin receptors, J. Exp. Med., 160, 1102, 10.1084/jem.160.4.1102 · DOI
  51. Schaefer, 2001, Observation of antigen-dependent CD8+ T-cell/ dendritic cell interactions in vivo, Cell. Immunol., 214, 110, 10.1006/cimm.2001.1895 · DOI · Paper page
  52. Schneider, 2005, Two-photon activation and excitation properties of PA-GFP in the 720-920-nm region, Biophys. J., 89, 1346, 10.1529/biophysj.104.054502 · DOI
  53. Schwickert, 2007, In vivo imaging of germinal centres reveals a dynamic open structure, Nature, 446, 83, 10.1038/nature05573 · DOI · Paper page
  54. Shih, 2002, Role of antigen receptor affinity in T cell-independent antibody responses in vivo, Nat. Immunol., 3, 399, 10.1038/ni776 · DOI
  55. Shokat, 1995, Antigen-induced B-cell death and elimination during germinal-centre immune responses, Nature, 375, 334, 10.1038/375334a0 · DOI · Paper page
  56. Suzuki, 2009, Visualizing B cell capture of cognate antigen from follicular dendritic cells, J. Exp. Med., 206, 1485, 10.1084/jem.20090209 · DOI · Paper page
  57. Tarlinton, 2008, Evolution in miniature: selection, survival and distribution of antigen reactive cells in the germinal centre, Immunol. Cell Biol., 86, 133, 10.1038/sj.icb.7100148 · DOI
  58. Tarlinton, 2000, Dissecting affinity maturation: a model explaining selection of antibody-forming cells and memory B cells in the germinal centre, Immunol. Today, 21, 436, 10.1016/S0167-5699(00)01687-X · DOI
  59. Tomura, 2008, Monitoring cellular movement in vivo with photoconvertible fluorescence protein “Kaede” transgenic mice, Proc. Natl. Acad. Sci. USA, 105, 10871, 10.1073/pnas.0802278105 · DOI · Paper page
  60. Vinuesa, 2005, Follicular B helper T cells in antibody responses and autoimmunity, Nat. Rev. Immunol., 5, 853, 10.1038/nri1714 · DOI
  61. Zhu, 2004, Analysis of the major patterns of B cell gene expression changes in response to short-term stimulation with 33 single ligands, J. Immunol., 173, 7141, 10.4049/jimmunol.173.12.7141 · DOI
  62. Aida, Y., and Pabst, M.J. (1990). Removal of endotoxin from protein solutions by phase separation using Triton X-114. J. Immunol. Methods 132, 191–195. · DOI · Paper page
  63. Allen, C.D., Okada, T., Tang, H.L., and Cyster, J.G. (2007). Imaging of germinal center selection events during affinity maturation. Science 315, 528–531. · DOI
  64. Brochet, X., Lefranc, M.P., and Giudicelli, V. (2008). IMGT/V-QUEST: the highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysis. Nucleic Acids Res. 36 (Web Server issue), W503-8. · DOI
  65. Huang, W., Sherman, B.T., and Lempicki, R.A. (2009). Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4, 44–57. · DOI · Paper page
  66. Lindquist, R.L., Shakhar, G., Dudziak, D., Wardemann, H., Eisenreich, T., Dustin, M.L., and Nussenzweig, M.C. (2004). Visualizing dendritic cell networks in vivo. Nat. Immunol. 5, 1243–1250. · DOI
  67. Mootha, V.K., Lindgren, C.M., Eriksson, K.F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstråle, M., Laurila, E., et al. (2003). PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat. Genet. 34, 267–273. · DOI · Paper page
  68. Reich, M., Liefeld, T., Gould, J., Lerner, J., Tamayo, P., and Mesirov, J.P. (2006). GenePattern 2.0. Nat. Genet. 38, 500–501. · DOI
  69. Shaner, N.C., Campbell, R.E., Steinbach, P.A., Giepmans, B.N., Palmer, A.E., and Tsien, R.Y. (2004). Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein. Nat. Biotechnol. 22, 1567–1572. · DOI · Paper page
  70. Subramanian, A., Tamayo, P., Mootha, V.K., Mukherjee, S., Ebert, B.L., Gillette, M.A., Paulovich, A., Pomeroy, S.L., Golub, T.R., Lander, E.S., and Mesirov, J.P. (2005). Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. USA 102, 15545–15550. · DOI · Paper page
  71. Xie, X., Lu, J., Kulbokas, E.J., Golub, T.R., Mootha, V., Lindblad-Toh, K., Lander, E.S., and Kellis, M. (2005). Systematic discovery of regulatory motifs in human promoters and 3′ UTRs by comparison of several mammals. Nature 434, 338–345. · DOI · Paper page

Cited by

Metadata

Authors
Victora, G. D., Schwickert, T. A., Fooksman, D. R., Kamphorst, A. O., Meyer-Hermann, M., Dustin, M. L., & Nussenzweig, M. C.
Venue
Cell
Publisher
Elsevier BV
Published
2010-11
Volume
143
Issue
4
Pages
592-605
ISSN
0092-8674
Cited by
1,238
References
6
Language
en

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