Antigen-driven selection in germinal centers as reflected by the shape characteristics of immunoglobulin gene lineage trees: A large-scale simulation study

Journal of Theoretical Biology

Volumn 255, Issue 2, 2008, Pages 210-222

  Shahaf, Gitit ^a   Barak, Michal ^a   Zuckerman, Neta S ^a   Swerdlin, Naamah ^a   Gorfine, Malka ^b   Mehr, Ramit ^a  

^a BAR ILAN UNIVERSITY   (Israel)

^b TECHNION ISRAEL INSTITUTE OF TECHNOLOGY   (Israel)

Author keywords

B lymphocyte; Germinal center (GC); Immunoglobulin (Ig) gene lineage trees; Mathematical model; Somatic hypermutation (SHM)

Indexed keywords

ANTIGEN;

ANTIGEN; CYTOLOGY; IMMUNE RESPONSE; MATURATION; MUTATION; NUMERICAL MODEL;

ARTICLE; B LYMPHOCYTE; CELL DIFFERENTIATION; CELL DIVISION; CELL LINEAGE; CELL MATURATION; CELL POPULATION; CELL PROLIFERATION; COMPUTER SIMULATION; GENE MUTATION; GERMINAL CENTER; HUMORAL IMMUNITY; IMMUNOGLOBULIN GENE; MATHEMATICAL MODEL; PRIORITY JOURNAL;

ANTIBODY DIVERSITY; ANTIGENS; B-LYMPHOCYTES; COMPUTER SIMULATION; GENES, IMMUNOGLOBULIN; GERMINAL CENTER; HUMANS; IMMUNOLOGIC MEMORY; MODELS, IMMUNOLOGICAL; RECEPTORS, ANTIGEN; SOMATIC HYPERMUTATION, IMMUNOGLOBULIN;

EID: 54249165359     PISSN: 00225193     EISSN: 10958541     Source Type: Journal    
DOI: 10.1016/j.jtbi.2008.08.005     Document Type: Article

References (83)

1. Abraham R.S., et al. Novel analysis of clonal diversification in blood B cell and bone marrow plasma cell clones in immunoglobulin light chain amyloidosis. J. Clin. Immunol. 27 (2007) 69-87
2. Allen C.D., et al. Imaging of germinal center selection events during affinity maturation. Science 315 (2007) 528-531
3. Allen C.D., et al. Germinal-center organization and cellular dynamics. Immunity 27 (2007) 190-202 (Review)
4. Banerjee M., et al. Age- and tissue-specific differences in human germinal center B cell selection revealed by analysis of IgVH gene hypermutation and lineage trees. Eur. J. Immunol. 32 (2002) 1947-1957
5. Berek C., and Milstein C. Mutation drift and repertoire shift in the maturation of the immune response. Immunol. Rev. 96 (1987) 23-41
6. Berek C., et al. Maturation of the immune response in germinal centers. Cell 67 (1991) 1121-1129
7. Bernstein R.M., et al. Complex mechanisms for inhibition of immunoglobulin gene expression in a germinal center B cell line. Mol. Immunol. 41 (2004) 63-72
8. Beyer T., et al. A possible role of chemotaxis in germinal center formation. Int. Immunol. 14 (2002) 1369-1381
9. Bolland D., and Corcoran A. Somatic hypermutation is a matter of choice. Nat. Immunol. 8 (2007) 677-679
10. Bose B., and Sinha S. Problems in using statistical analysis of replacement and silent mutations in antibody genes for determining antigen-driven affinity selection. Immunology 116 (2005) 172-183
11. Box G.E.P., and Cox D.R. An analysis of transformations. J. R. Stat. Soc. Ser. B 26 (1964) 211-246
12. Bross L., et al. Somatic hypermutation does not require Rad54 and Rad54B-mediated homologous recombination. Eur. J. Immunol. 33 (2003) 352-357
13. Chalouni C., et al. Human germinal center B cells differ from naive and memory B cells by their aggregated MHC class II-rich compartments lacking HLA-DO. Int. Immunol. 15 (2003) 457-466
14. Christopher D.C., et al. Germinal center dark and light zone organization is mediated by CXCR4 and CXCR5. Nat. Immunol. 5 (2004) 943-952
15. Dunn-Walters D.K., et al. Hypermutation, diversity and dissemination of human intestinal lamina propria plasma cells. Eur. J. Immunol. 27 (1997) 2959-2964
16. Dunn-Walters D.K., et al. Sequence analysis of human IgVH genes indicates that ileal lamina propria plasma cells are derived from Peyer's patches. Eur. J. Immunol. 27 (1997) 463-467
17. Dunn-Walters D.K., et al. Base-specific sequences that bias somatic hypermutation deduced by analysis of out-of-frame human IgVH genes. J. Immunol. 160 (1998) 2360-2364
18. Dunn-Walters D.K., et al. The dynamics of germinal centre selection as measured by graph-theoretical analysis of mutational lineage trees. Dev. Immunol. 9 (2002) 233-245
19. Dunn-Walters D.K., et al. Effects of age on antibody affinity maturation. Biochem. Soc. Trans. 31 (2003) 447-448
20. Dunn-Walters D.K., et al. Immune system learning and memory quantified by graphical analysis of B-lymphocyte phylogenetic trees. BioSystems 76 (2004) 141-155
21. Foster S.J., et al. Somatic hypermutation of VkJk rearrangements: targeting of RGYW motifs on both DNA strands and preferential selection of mutated codons within RGYW motifs. Eur. J. Immunol. 29 (1999) 4011-4021
22. Goodman L.A., and Kruskal W.H. Measures of association for cross classifications. J. Am. Stat. Assoc. 49 (1954) 732-764
23. Han S., et al. FTY720 suppresses humoral immunity by inhibiting germinal center reaction. Blood 104 (2004) 4129-4133
24. Hangartner L., et al. Antiviral antibody responses: the two extremes of a wide spectrum. Nat. Rev. Immunol. 6 (2006) 231-243
25. Hauser A.E., et al. In vivo imaging studies shed light on germinal-centre development. Nat. Rev. Immunol. 7 (2007) 499-504
26. Heyman B. Regulation of antibody responses via antibodies, complement, and Fc receptors. Annu. Rev. Immunol. 18 (2000) 709-737
27. Hjelm F., et al. antibody-mediated regulation of the immune response. Scand. J. Immunol. 64 (2006) 177-184
28. Honjo T., et al. Mechanism of class switch recombination: linkage with somatic hypermutation. Ann. Rev. Immunol. 20 (2002) 165-196
29. Jacob J., and Kelsoe G. In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl) acetyl. II. A common clonal origin for periarteriolar lymphoid sheath-associated foci and germinal centers. J. Exp. Med. 176 (1992) 679-687
30. Jacob J., et al. Intraclonal generation of antibody mutants in germinal centres. Nature 354 (1991) 389-392
31. Jacob J., et al. 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 (1993) 1293-1307
32. Kelsoe G. The germinal center: a crucible for lymphocyte selection. Semin. Immunol. 8 (1996) 179-184
33. Kepler T.B., and Perelson A.S. Cyclic re-entry of germinal center B cells and the efficiency of affinity maturation. Immunol. Today 14 (1993) 412-415
34. Kesmir C., and De Boer R.J. A mathematical model on germinal center kinetics and termination. J. Immunol. 163 (1999) 2463-2469
35. Kesmir C., and De Boer R.J. A spatial model of germinal center reactions: cellular adhesion based sorting of B cells results in efficient affinity maturation. J. Theor. Biol. 222 (2003) 9-22
36. Kleinstein S.H., and Singh J.P. Toward quantitative simulation of germinal center dynamics: biological and modeling insights from experimental validation. J. Theor. Biol. 211 (2001) 253-275
37. Kleinstein S.H., and Singh J.P. Why are there so few key mutant clones? The influence of stochastic selection and blocking on affinity maturation in the germinal center. Int. Immunol. 15 (2003) 871-884
38. Kleinstein S.H., et al. Estimating hypermutation rates from clonal tree data. J. Immunol. 171 (2003) 4639-4649
39. Kocks C., and Rajewsky K. Stepwise intraclonal maturation of antibody affinity through somatic hypermutation. Proc. Natl. Acad. Sci. 85 (1988) 8206-8210
40. Lebecque S.G., and Gearhart P.J. Boundaries of somatic mutation generating the sheep immunoglobulin repertoire are an antigen independent process. Cell 80 (1990) 115-125
41. Liu Y.J., et al. Sites of specific B cell activation in primary and secondary responses to T cell-dependent and T cell-independent antigens. Eur. J. Immunol. 21 (1991) 2951-2962
42. Longo N.S., and Lipsky P.E. Why do B cells mutate their immunoglobulin receptors?. Trends Immunol. 27 (2006) 374-380
43. Lu L., and Osmond D.G. Apoptosis during B lymphopoiesis in mouse bone marrow. J. Immunol. 158 11 (1997) 5136-5145
44. MacLennan I.C.M. Germinal centers. Annu. Rev. Immunol. 12 (1994) 117-139
45. Magori-Cohen R., et al. Mutation parameters from DNA sequence data using graph theoretic measures on lineage trees. Bioinformatics 22 14 (2006) e332-e340
46. Manser T. Evolution of antibody structure during the immune response. J. Exp. Med. 170 (1989) 1211-1230
47. Manske M.K., et al. Quantitative analysis of clonal bone marrow CD19+ B cells: use of B cell lineage trees to delineate their role in the pathogenesis of light chain amyloidosis. Clin. Immunol. 120 (2006) 106-120
48. Mehr R., et al. Analysis of mutational lineage trees from sites of primary and secondary immunoglobulin gene diversification in rabbits and chickens. J. Immunol. 172 (2004) 4790-4796
49. Meyer-Hermann M. A mathematical model for the germinal center morphology and affinity maturation. J. Theor. Biol. 216 (2002) 273-300
50. Meyer-Hermann M. Does recycling in germinal centers exist?. Immunol. Cell Biol. 80 (2002) 30-35
51. Meyer-Hermann M. A concerted action of b cell selection mechanisms. Adv. Complex Systems 10 (2007) 557-580
52. Meyer-Hermann M., and Beyer T. Conclusions from two model concepts on germinal center dynamics and morphology. Dev. Immunol. 9 (2002) 203-214
53. Meyer-Hermann M., and Beyer T. The type of seeder cells determines the efficiency of germinal center reactions. Bull. Math. Biol. 66 (2004) 125-141
54. Meyer-Hermann M., et al. Recycling probability and dynamical properties of germinal center reactions. J. Theor. Biol. 210 (2001) 265-285
55. Michael N., et al. Effects of sequence and structure on the hypermutability of immunoglobulin genes. Immunity 16 (2002) 123-134
56. Monson N.L., et al. Targeting and selection of mutations in human Vlambda-rearrangements. Eur. J. Immunol. 30 (2000) 1597-1605
57. Nagelkerke N.J.D. A note on a general definition of the coefficient of determination. Biometrika 78 (1991) 691-692
58. Odegard V.H., and Schatz D.G. Targeting of somatic hypermutation. Nat. Rev. Immunol. 6 (2006) 573-583
59. Oprea M., and Kepler T.B. Genetic plasticity of V genes under somatic hypermutation: Statistical analyses using a new resampling-based methodology. Gen. Res. 9 (1999) 1294-1304
60. Oprea M., and Perelson A.S. Exploring the mechanisms of primary antibody responses to T cell-dependent antigens. J. Theor. Biol. 181 (1996) 215-236
61. Oprea M., et al. Somatic mutation leads to efficient affinity maturation when centrocytes recycle back to centroblasts. J. Immunol. 158 (1997) 5155-5162
62. Phan T.G., et al. Subcapsular encounter and complement-dependent transport of immune complexes by lymph node B cells. Nat. Immunol. 8 (2007) 992-1000
63. Schiaffella E., et al. Gene conversion and hypermutation during diversification of VH sequences in developing splenic germinal centers of immunized rabbits. J. Immunol. 162 (1999) 3984-3995
64. Schwickert T.A., et al. In vivo imaging of germinal centres reveals a dynamic open structure. Nature 446 (2007) 83-87
65. Sehgal D., et al. Analysis of single B cells by PCR reveals rearranged VH with germline sequences in spleen of immunized rabbits: implications for B cell repertoire maintenance and renewal. J. Immunol. 161 (1998) 5347-5356
66. Sehgal D., et al. Generation of heterogeneous rabbit anti-DNP antibodies by gene conversion and hypermutation of rearranged VL and VH genes during clonal expansion of B cells in splenic germinal centers. Eur. J. Immunol. 30 (2000) 3634-3644
67. Sehgal D., et al. Distinct clonal diversification patterns in young appendix compared to antigen-specific splenic clones. J. Immunol. 168 (2002) 5424-5433
68. Shahaf G., et al. Screening of alternative models for transitional B cell maturation. Intl. Immunol. 16 (2004) 1081-1090
69. Shannon M., and Mehr R. Reconciling repertoire shift with affinity maturation: the role of deleterious mutations. J. Immunol. 162 (1999) 3950-3956
70. Shlomchik M., et al. Clone: a Monte-Carlo computer simulation of B cell clonal expansion, somatic mutation, and antigen-driven selection. Curr. Top. Microbiol. Immunol. 229 (1998) 173-197
71. Somers R.H. A new asymmetric measure of association for ordinal variables. Am. Sociolog. Rev. 27 (1962) 799-811
72. Song H., et al. Regulation of VH gene repertoire and somatic mutation in germinal centre B cells by passively administered antibody. Immunology 98 (1999) 258-266
73. Spencer J., and Dunn-Walters D.K. Hypermutation at A-T base pairs: the A nucleotide replacement spectrum is affected by adjacent nucleotides and there is no reverse complimentarity of sequences flanking mutated A and T nucleotides. J. Immunol. 175 (2005) 5170-5177
74. Spencer J., et al. Characteristics of sequences around individual nucleotide substitutions in IgVH genes suggest different GC and AT mutators. J. Immunol. 162 (1999) 6596-6601
75. Steiman-Shimony A., et al. Immunoglobulin variable-region gene mutational lineage tree analysis: application to autoimmune diseases. Autoimmun. Rev. 5 (2006) 242-251
76. Sulzer B., et al. Memory in idiotypic networks due to competition between proliferation and differentiation. Bull. Math. Biol. 55 (1993) 1133-1182
77. van Galen J.C., et al. Distinct expression patterns of polycomb oncoproteins and their binding partners during the germinal center reaction. Eur. J. Immunol. 34 (2004) 1870-1881
78. Vora K.A., et al. Contrasting the in situ behavior of a memory B cell clone during primary and secondary immune responses. J. Immunol. 163 (1999) 4315-4327
79. Vora K.A., et al. Cutting edge: germinal centers formed in the absence of B cell-activating factor belonging to the TNF family exhibit impaired maturation and function. J. Immunol. 171 (2003) 547-551
80. Winter D.B., et al. Normal somatic hypermutation of Ig genes in the absence of 8-hydroxyguanine-DNA glycosylase. J. Immunol. 170 (2003) 5558-5562
81. Woodland R.T., and Schmidt M.R. Homeostatic proliferation of B cells. Semin. Immunol. 17 3 (2005) 209-217 (Review)
82. Xiao Y., et al. CD27 is acquired by primed B cells at the centroblast stage and promotes germinal center formation. J. Immunol. 172 (2004) 7432-7441
83. Young L.C. On randomness in ordered sequences. Ann. Math. Stat. 12 (1941) 293-300