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Germinal Center Dynamics Revealed by Multiphoton Microscopy with a Photoactivatable Fluorescent Reporter
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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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., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
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) · Nature Genetics · doi:10.1038/ng1180 · Cited by 10,197
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Dennis, G., Sherman, B. T., Hosack, D. A., Yang, J., Gao, W., Lane, H. C., & Lempicki, R. A. (2003) · Genome Biology · doi:10.1186/gb-2003-4-5-p3 · Cited by 9,327
Shaner, N. C., Campbell, R. E., Steinbach, P. A., Giepmans, B. N. G., Palmer, A. E., & Tsien, R. Y. (2004) · Nature Biotechnology · doi:10.1038/nbt1037 · Cited by 4,619
Xie, X., Lu, J., Kulbokas, E. J., Golub, T. R., Mootha, V., Lindblad-Toh, K., Lander, E. S., & Kellis, M. (2005) · Nature · doi:10.1038/nature03441 · Cited by 1,872
Vinuesa, C. G., Cook, M. C., Angelucci, C., Athanasopoulos, V., Rui, L., Hill, K. M., Yu, D., Domaschenz, H., Whittle, B., Lambe, T., et al. (2005) · Nature · doi:10.1038/nature03555 · Cited by 862
Research works printed but not linked: 71
- 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
- Allen, 2007, Germinal-center organization and cellular dynamics, Immunity, 27, 190, 10.1016/j.immuni.2007.07.009 · DOI · Paper page
- Allen, 2007, Imaging of germinal center selection events during affinity maturation, Science, 315, 528, 10.1126/science.1136736 · DOI
- 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
- Basso, 2004, Tracking CD40 signaling during germinal center development, Blood, 104, 4088, 10.1182/blood-2003-12-4291 · DOI
- Batista, 2001, B cells acquire antigen from target cells after synapse formation, Nature, 411, 489, 10.1038/35078099 · DOI
- 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
- 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
- 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
- Delbos, 2005, Contribution of DNA polymerase eta to immunoglobulin gene hypermutation in the mouse, J. Exp. Med., 201, 1191, 10.1084/jem.20050292 · DOI
- Depoil, 2005, Immunological synapses are versatile structures enabling selective T cell polarization, Immunity, 22, 185, 10.1016/j.immuni.2004.12.010 · DOI
- Eisen, 1964, Variations in affinities of antibodies during the immune response, Biochemistry, 3, 996, 10.1021/bi00895a027 · DOI · Paper page
- Figge, 2008, Deriving a germinal center lymphocyte migration model from two-photon data, J. Exp. Med., 205, 3019, 10.1084/jem.20081160 · DOI
- Fooksman, 2010, Development and migration of plasma cells in the mouse lymph node, Immunity, 33, 118, 10.1016/j.immuni.2010.06.015 · DOI
- Germain, 2006, Dynamic imaging of the immune system: progress, pitfalls and promise, Nat. Rev. Immunol., 6, 497, 10.1038/nri1884 · DOI · Paper page
- 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
- 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
- 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
- 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
- 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
- Hauser, 2007, In vivo imaging studies shed light on germinal-centre development, Nat. Rev. Immunol., 7, 499, 10.1038/nri2120 · DOI
- 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
- 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
- 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
- Kamphorst, 2010, Route of antigen uptake differentially impacts presentation by dendritic cells and activated monocytes, J. Immunol., 185, 3426, 10.4049/jimmunol.1001205 · DOI
- 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
- 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
- Klein, 2008, Germinal centres: role in B-cell physiology and malignancy, Nat. Rev. Immunol., 8, 22, 10.1038/nri2217 · DOI
- Lanzavecchia, 1985, Antigen-specific interaction between T and B cells, Nature, 314, 537, 10.1038/314537a0 · DOI · Paper page
- Liu, 1989, Mechanism of antigen-driven selection in germinal centres, Nature, 342, 929, 10.1038/342929a0 · DOI · Paper page
- 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
- MacLennan, 1994, Germinal centers, Annu. Rev. Immunol., 12, 117, 10.1146/annurev.iy.12.040194.001001 · DOI · Paper page
- Manser, 2004, Textbook germinal centers?, J. Immunol., 172, 3369, 10.4049/jimmunol.172.6.3369 · DOI
- 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
- Meyer-Hermann, 2001, Recycling probability and dynamical properties of germinal center reactions, J. Theor. Biol., 210, 265, 10.1006/jtbi.2001.2297 · DOI
- 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
- Meyer-Hermann, 2006, An analysis of B cell selection mechanisms in germinal centers, Math. Med. Biol., 23, 255, 10.1093/imammb/dql012 · DOI
- 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
- 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
- Nieuwenhuis, 1984, Functional anatomy of germinal centers, Am. J. Anat., 170, 421, 10.1002/aja.1001700315 · DOI
- 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
- Nussenzweig, 1967, Antihapten antibody specificity and L chain type, J. Exp. Med., 126, 727, 10.1084/jem.126.4.727 · DOI
- 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
- Patterson, 2002, A photoactivatable GFP for selective photolabeling of proteins and cells, Science, 297, 1873, 10.1126/science.1074952 · DOI · Paper page
- 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
- 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
- Pulendran, 1995, Soluble antigen can cause enhanced apoptosis of germinal-centre B cells, Nature, 375, 331, 10.1038/375331a0 · DOI
- Rajewsky, 1996, Clonal selection and learning in the antibody system, Nature, 381, 751, 10.1038/381751a0 · DOI
- 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
- 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
- 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
- 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
- Schwickert, 2007, In vivo imaging of germinal centres reveals a dynamic open structure, Nature, 446, 83, 10.1038/nature05573 · DOI · Paper page
- Shih, 2002, Role of antigen receptor affinity in T cell-independent antibody responses in vivo, Nat. Immunol., 3, 399, 10.1038/ni776 · DOI
- Shokat, 1995, Antigen-induced B-cell death and elimination during germinal-centre immune responses, Nature, 375, 334, 10.1038/375334a0 · DOI · Paper page
- 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
- 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
- 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
- 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
- Vinuesa, 2005, Follicular B helper T cells in antibody responses and autoimmunity, Nat. Rev. Immunol., 5, 853, 10.1038/nri1714 · DOI
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Reich, M., Liefeld, T., Gould, J., Lerner, J., Tamayo, P., and Mesirov, J.P. (2006). GenePattern 2.0. Nat. Genet. 38, 500–501. · DOI
- 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
- 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
- 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
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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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- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 989 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
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