Is there a typical germinal center? A large-scale immunohistological study on the cellular composition of germinal centers during the hapten-carrier-driven primary immune response in mice

Journal of Immunology

Volumn 187, Issue 12, 2011, Pages 6185-6196

  Wittenbrink, Nicole ^a,b   Klein, Anke ^a,b,d   Weiser, Armin A ^a,b   Schuchhardt, Johannes ^c   Or Guil, Michal ^a,b  

^a HUMBOLDT UNIVERSITY   (Germany)

^b CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^c MICRODISCOVERY GMBH   (Germany)

^d UNIVERSITY OF LEIPZIG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

2 PHENYL 5 OXAZOLONE; OXAZOLONE; SERUM ALBUMIN; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BAGG ALBINO MOUSE; CELL COMPOSITION; CELL DENSITY; CELL LOSS; CELL PROLIFERATION; CONTROLLED STUDY; GERMINAL CENTER; HAPTEN CARRIER COMPLEX; IMAGE ANALYSIS; IMMUNOHISTOLOGY; MACROPHAGE; MOUSE; NONHUMAN; PRIMARY IMMUNE RESPONSE; PRIORITY JOURNAL; SPLEEN; T LYMPHOCYTE;

ANIMALS; APOPTOSIS; B-LYMPHOCYTE SUBSETS; CARRIER PROTEINS; CELL COMPARTMENTATION; CELL PROLIFERATION; CLONE CELLS; CROSS-SECTIONAL STUDIES; FLUORESCENT ANTIBODY TECHNIQUE; GERMINAL CENTER; HAPTENS; IMMUNOHISTOCHEMISTRY; MACROPHAGES; MICE; MICE, INBRED BALB C; MICROSCOPY, CONFOCAL; OXAZOLONE; SERUM ALBUMIN; SPLEEN; T-LYMPHOCYTE SUBSETS;

EID: 83755184217     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1101440     Document Type: Article

References (65)

1. MacLennan, I. C. 1994. Germinal centers. Annu. Rev. Immunol. 12: 117-139. (Pubitemid 24140411)
2. Tarlinton, D. M. 2008. Evolution in miniature: selection, survival and distribution of antigen reactive cells in the germinal centre. Immunol. Cell Biol. 86: 133-138. (Pubitemid 351301762)
3. Alexander, C. M., L. T. Tygrett, A. W. Boyden, K. L. Wolniak, K. L. Legge, and T. J. Waldschmidt. 2011. T regulatory cells participate in the control of germinal centre reactions. Immunology 133: 452-468.
4. Shinall, S. M., M. Gonzalez-Fernandez, R. J. Noelle, and T. J. Waldschmidt. 2000. Identification of murine germinal center B cell subsets defined by the expression of surface isotypes and differentiation antigens. J. Immunol. 164: 5729-5738. (Pubitemid 30389815)
5. Wolniak, K. L., S. M. Shinall, and T. J. Waldschmidt. 2004. The germinal center response. Crit. Rev. Immunol. 24: 39-65. (Pubitemid 39655011)
6. Grouard, G., I. Durand, L. Filgueira, J. Banchereau, and Y. J. Liu. 1996. Dendritic cells capable of stimulating T cells in germinal centres. Nature 384: 364-367. (Pubitemid 26408519)
7. Kim, M. Y., F. M. Gaspal, H. E. Wiggett, F. M. McConnell, A. Gulbranson-Judge, C. Raykundalia, L. S.Walker, M. D. Goodall, and P. J. Lane. 2003. CD4(+) CD3(-) accessory cells costimulate primed CD4 T cells through OX40 and CD30 at sites where T cells collaborate with B cells. Immunity 18: 643-654. (Pubitemid 36588581)
8. Carroll, M. C. 1998. The role of complement and complement receptors in induction and regulation of immunity. Annu. Rev. Immunol. 16: 545-568. (Pubitemid 28183376)
9. Liu, Y. J., J. Xu, O. de Bouteiller, C. L. Parham, G. Grouard, O. Djossou, B. de Saint-Vis, S. Lebecque, J. Banchereau, and K. W. Moore. 1997. Follicular dendritic cells specifically express the long CR2/CD21 isoform. J. Exp. Med. 185: 165-170. (Pubitemid 27039450)
10. Qin, D., J.Wu, K. A. Vora, J. V. Ravetch, A. K. Szakal, T. Manser, and J. G. Tew. 2000. Fc gamma receptor IIB on follicular dendritic cells regulates the B cell recall response. J. Immunol. 164: 6268-6275. (Pubitemid 30408807)
11. Liu, Y. J., G. D. Johnson, J. Gordon, and I. C. MacLennan. 1992. Germinal centres in T-cell-dependent antibody responses. Immunol. Today 13: 17-21.
12. van Eijk, M., J. P. Medema, and C. de Groot. 2001. Cutting edge: cellular Fas-associated death domain-like IL-1-converting enzyme-inhibitory protein protects germinal center B cells from apoptosis during germinal center reactions. J. Immunol. 166: 6473-6476.
13. Kosco, M. H., E. Pflugfelder, and D. Gray. 1992. Follicular dendritic cell-dependent adhesion and proliferation of B cells in vitro. J. Immunol. 148: 2331-2339.
14. Liu, Y. J., O. de Bouteiller, and I. Fugier-Vivier. 1997. Mechanisms of selection and differentiation in germinal centers. Curr. Opin. Immunol. 9: 256-262. (Pubitemid 27190128)
15. Meyer-Hermann, M. E., P. K. Maini, and D. Iber. 2006. An analysis of B cell selection mechanisms in germinal centers. Math. Med. Biol. 23: 255-277. (Pubitemid 44592717)
16. Vinuesa, C. G., S. G. Tangye, B. Moser, and C. R. Mackay. 2005. Follicular B helper T cells in antibody responses and autoimmunity. Nat. Rev. Immunol. 5: 853-865. (Pubitemid 41581667)
17. Hardie, D. L., G. D. Johnson, M. Khan, and I. C. MacLennan. 1993. Quantitative analysis of molecules which distinguish functional compartments within germinal centers. Eur. J. Immunol. 23: 997-1004. (Pubitemid 23120156)
18. Victora, G. D., T. A. Schwickert, D. R. Fooksman, A. O. Kamphorst, M. Meyer-Hermann, M. L. Dustin, and M. C. Nussenzweig. 2010. Germinal center dynamics revealed by multiphoton microscopy with a photoactivatable fluorescent reporter. Cell 143: 592-605.
19. Gaipl, U. S., R. E. Voll, A. Sheriff, S. Franz, J. R. Kalden, and M. Herrmann. 2005. Impaired clearance of dying cells in systemic lupus erythematosus. Autoimmun. Rev. 4: 189-194. (Pubitemid 40704701)
20. Smith, J. P., M. H. Kosco, J. G. Tew, and A. K. Szakal. 1988. Thy-1 positive tingible body macrophages (TBM) in mouse lymph nodes. Anat. Rec. 222: 380-390. (Pubitemid 19037108)
21. Smith, J. P., A. M. Lister, J. G. Tew, and A. K. Szakal. 1991. Kinetics of the tingible body macrophage response in mouse germinal center development and its depression with age. Anat. Rec. 229: 511-520.
22. Wang, Y., and R. H. Carter. 2005. CD19 regulates B cell maturation, proliferation, and positive selection in the FDC zone of murine splenic germinal centers. Immunity 22: 749-761. (Pubitemid 40814505)
23. Rahman, Z. S., S. P. Rao, S. L. Kalled, and T. Manser. 2003. Normal induction but attenuated progression of germinal center responses in BAFF and BAFF-R signaling-deficient mice. J. Exp. Med. 198: 1157-1169. (Pubitemid 37323381)
24. Takahashi, Y., D. M. Cerasoli, J. M. Dal Porto, M. Shimoda, R. Freund, W. Fang, D. G. Telander, E. N. Malvey, D. L. Mueller, T. W. Behrens, and G. Kelsoe. 1999. Relaxed negative selection in germinal centers and impaired affinity maturation in bcl-xL transgenic mice. J. Exp. Med. 190: 399-410.
25. Wittenbrink, N., T. S. Weber, A. Klein, A. A. Weiser, W. Zuschratter, M. Sibila, J. Schuchhardt, and M. Or-Guil. 2010. Broad volume distributions indicate nonsynchronized growth and suggest sudden collapses of germinal center B cell populations. J. Immunol. 184: 1339-1347.
26. Faro, J., and M. OrGuil. 2011. Reassessing germinal center reaction concepts. In Mathematical Models in Immune Cell Biology. G. Lythe and C. Molina-París, eds. Springer Press, New York, p. 424.
27. Berek, C., G. M. Griffiths, and C. Milstein. 1985. Molecular events during maturation of the immune response to oxazolone. Nature 316: 412-418. (Pubitemid 16238451)
28. Allen, C. D., K. M. Ansel, C. Low, R. Lesley, H. Tamamura, N. Fujii, and J. G. Cyster. 2004. Germinal center dark and light zone organization is mediated by CXCR4 and CXCR5. Nat. Immunol. 5: 943-952. (Pubitemid 39276239)
29. Hauser, A. E., T. Junt, T. R. Mempel, M. W. Sneddon, S. H. Kleinstein, S. E. Henrickson, U. H. von Andrian, M. J. Shlomchik, and A. M. Haberman. 2007. Definition of germinal-center B cell migration in vivo reveals predominant intrazonal circulation patterns. Immunity 26: 655-667. (Pubitemid 46756352)
30. Schwickert, T. A., R. L. Lindquist, G. Shakhar, G. Livshits, D. Skokos, M. H. Kosco-Vilbois, M. L. Dustin, and M. C. Nussenzweig. 2007. In vivo imaging of germinal centres reveals a dynamic open structure. Nature 446: 83-87. (Pubitemid 46348044)
31. Abramoff, M. D., P. J. Magelhaes, and S. J. Ram. 2004. Image processing with ImageJ. Biophotonics International 11: 36-42.
32. Luzina, I. G., S. P. Atamas, C.E. Storrer, L. C. daSilva, G. Kelsoe, J. C. Papadimitriou, and B. S. Handwerger. 2001. Spontaneous formation of germinal centers in autoimmune mice. J. Leukoc. Biol. 70: 578-584. (Pubitemid 32954768)
33. Ninomiya, E., Y. Ito, M. A. Shibata, K. Kawashima, T. Sakamoto, E. Maruyama, H. Doi, K. Tokitsu, and Y. Otsuki. 2003. The activation of caspase-3 and DNA fragmentation in B cells phagocytosed by macrophages. Med. Electron Microsc. 36: 87-93. (Pubitemid 36898473)
34. Wolniak, K. L., R. J. Noelle, and T. J. Waldschmidt. 2006. Characterization of (4-hydroxy-3-nitrophenyl)acetyl (NP)-specific germinal center B cells and antigen-binding B220- cells after primary NP challenge in mice. J. Immunol. 177: 2072-2079. (Pubitemid 44200964)
35. Scholzen, T., and J. Gerdes. 2000. The Ki-67 protein: from the known and the unknown. J. Cell. Physiol. 182: 311-322. (Pubitemid 30054364)
36. Linterman, M. A., L. Beaton, D. Yu, R. R. Ramiscal, M. Srivastava, J. J. Hogan, N. K. Verma, M. J. Smyth, R. J. Rigby, and C. G. Vinuesa. 2010. IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses. J. Exp. Med. 207: 353-363.
37. Taylor, P. R., M. C. Pickering, M. H. Kosco-Vilbois, M. J. Walport, M. Botto, S. Gordon, and L. Martinez-Pomares. 2002. The follicular dendritic cell restricted epitope, FDC-M2, is complement C4; localization of immune complexes in mouse tissues. Eur. J. Immunol. 32: 1888-1896. (Pubitemid 34814544)
38. Camacho, S. A., M. H. Kosco-Vilbois, and C. Berek. 1998. The dynamic structure of the germinal center. Immunol. Today 19: 511-514. (Pubitemid 28518029)
39. Kepler, T. B., and A. S. Perelson. 1993. Cyclic re-entry of germinal center B cells and the efficiency of affinity maturation. Immunol. Today 14: 412-415. (Pubitemid 23226229)
40. MacLennan, I. C., G. D. Johnson, Y. J. Liu, and J. Gordon. 1991. The heterogeneity of follicular reactions. Res. Immunol. 142: 253-257.
41. Oprea, M., and A. S. Perelson. 1997. Somatic mutation leads to efficient affinity maturation when centrocytes recycle back to centroblasts. J. Immunol. 158: 5155-5162. (Pubitemid 127681217)
42. Han, S., K. Hathcock, B. Zheng, T. B. Kepler, R. Hodes, and G. Kelsoe. 1995. Cellular interaction in germinal centers. Roles of CD40 ligand and B7-2 in established germinal centers. J. Immunol. 155: 556-567.
43. Fillatreau, S., and D. Gray. 2003. T cell accumulation in B cell follicles is regulated by dendritic cells and is independent of B cell activation. J. Exp. Med. 197: 195-206. (Pubitemid 36152314)
44. Lentz, V. M., and T. Manser. 2001. Cutting edge: germinal centers can be induced in the absence of T cells. J. Immunol. 167: 15-20. (Pubitemid 32567755)
45. de Vinuesa, C. G., M. C. Cook, J. Ball, M. Drew, Y. Sunners, M. Cascalho, M. Wabl, G. G. Klaus, and I. C. MacLennan. 2000. Germinal centers without T cells. J. Exp. Med. 191: 485-494.
46. Gulbranson-Judge, A., and I. MacLennan. 1996. Sequential antigen-specific growth of T cells in the T zones and follicles in response to pigeon cytochrome c. Eur. J. Immunol. 26: 1830-1837. (Pubitemid 26283158)
47. Linton, P. J., J. Harbertson, and L. M. Bradley. 2000. A critical role for B cells in the development of memory CD4 cells. J. Immunol. 165: 5558-5565.
48. van Essen, D., P. Dullforce, T. Brocker, and D. Gray. 2000. Cellular interactions involved in Th cell memory. J. Immunol. 165: 3640-3646. (Pubitemid 32057268)
49. Zheng, B., S. Han, Q. Zhu, R. Goldsby, and G. Kelsoe. 1996. Alternative pathways for the selection of antigen-specific peripheral T cells. Nature 384: 263-266. (Pubitemid 26396975)
50. Allen, C. D., T. Okada, and J. G. Cyster. 2007. Germinal-center organization and cellular dynamics. Immunity 27: 190-202. (Pubitemid 47284923)
51. Brachtel, E. F., M. Washiyama, G. D. Johnson, K. Tenner-Racz, P. Racz, and I. C. MacLennan. 1996. Differences in the germinal centres of palatine tonsils and lymph nodes. Scand. J. Immunol. 43: 239-247. (Pubitemid 26096685)
52. Flemming, W. 1885. Studien über Regeneration der Gewebe. Arch Mikrosk Anat 24: 355.
53. Congdon, C. C., and J. W. Goodman. 1961. Changes in lymphatic tissues during foreign tissue transplantation. In International Symposium on Tissue Transplantation. A. P. Christoffanini and G. Hoecker, eds. Universidad de Chile, Santiago. p. 181.
54. Swartzendruber, D. C., and C. C. Congdon. 1963. Electron microscope observations on tingible body macrophages in mouse spleen. J. Cell Biol. 19: 641-646.
55. Hughes, R. C. 1994. Mac-2: a versatile galactose-binding protein of mammalian tissues. Glycobiology 4: 5-12. (Pubitemid 24060512)
56. Ho, M. K., and T. A. Springer. 1982. Mac-1 antigen: quantitative expression in macrophage populations and tissues, and immunofluorescent localization in spleen. J. Immunol. 128: 2281-2286. (Pubitemid 12086524)
57. Garner, R. E., A. P. Malick, A. D. Yurochko, and K. D. Elgert. 1987. Shifts in macrophage (M phi) surface phenotypes during tumor growth: association of Mac-2+ and Mac-3+ M phi with immunosuppressive activity. Cell. Immunol. 108: 255-268. (Pubitemid 17133845)
58. Malick, A. P., K. D. Elgert, R. E. Garner, and N. F. Adkinson, Jr. 1987. Prostaglandin E2 production by Mac-2+ macrophages: tumor-induced population shift. J. Leukoc. Biol. 42: 673-681. (Pubitemid 18004719)
59. Murn, J., O. Alibert, N. Wu, S. Tendil, and X. Gidrol. 2008. Prostaglandin E2 regulates B cell proliferation through a candidate tumor suppressor, Ptger4. J. Exp. Med. 205: 3091-3103.
60. Simkin, N. J., D. F. Jelinek, and P. E. Lipsky. 1987. Inhibition of human B cell responsiveness by prostaglandin E2. J. Immunol. 138: 1074-1081. (Pubitemid 17017887)
61. Smith, J. P., G. F. Burton, J. G. Tew, and A. K. Szakal. 1998. Tingible body macrophages in regulation of germinal center reactions. Dev. Immunol. 6: 285-294. (Pubitemid 28517785)
62. Jacob, J., J. Przylepa, C. Miller, and G. Kelsoe. 1993. In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. III. The kinetics of V region mutation and selection in germinal center B cells. J. Exp. Med. 178: 1293-1307. (Pubitemid 23277362)
63. Figge, M. T., A. Garin, M. Gunzer, M. Kosco-Vilbois, K. M. Toellner, and M. Meyer-Hermann. 2008. Deriving a germinal center lymphocyte migration model from two-photon data. J. Exp. Med. 205: 3019-3029.
64. Coles, H. S., J. F. Burne, and M. C. Raff. 1993. Large-scale normal cell death in the developing rat kidney and its reduction by epidermal growth factor. Development 118: 777-784. (Pubitemid 23232785)
65. Bursch, W., S. Paffe, B. Putz, G. Barthel, and R. Schulte-Hermann. 1990. Determination of the length of the histological stages of apoptosis in normal liver and in altered hepatic foci of rats. Carcinogenesis 11: 847-853. (Pubitemid 20150256)