Predicted and inferred waiting times for key mutations in the germinal centre reaction: Evidence for stochasticity in selection

Immunology and Cell Biology

Volumn 76, Issue 4, 1998, Pages 373-381

  Radmacher, Michael D ^a   Kelsoe, Garnett ^b   Kepler, Thomas B ^a  

^a NORTH CAROLINA STATE UNIVERSITY   (United States)

^b UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

Author keywords

B lymphocytes; Germinal centre; Immunoglobulins; Maximum likelihood estimates; Statistical models

Indexed keywords

IMMUNOGLOBULIN;

ANIMAL CELL; ARTICLE; CELL MATURATION; CELL MIGRATION; DNA SEQUENCE; GENE MUTATION; GENETIC SELECTION; GERMINAL CENTER; HUMORAL IMMUNITY; IMMUNE RESPONSE; MOLECULAR INTERACTION; NONHUMAN; PREDICTION; RECEPTOR AFFINITY; STOCHASTIC MODEL;

ANIMALS; CELL DIFFERENTIATION; GERMINAL CENTER; HUMANS; MUTATION; STOCHASTIC PROCESSES; TIME FACTORS;

ANIMALIA;

EID: 0031831107     PISSN: 08189641     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1440-1711.1998.00753.x     Document Type: Article

References (43)

1. Berek C, Berger A, Apel M. Maturation of the immune response in germinal centers. Cell 1991; 67: 1121-9.
2. Jacob J, Kelsoe G, Rajewsky K, Weiss U. Intraclonal generation of antibody mutants in germinal centres. Nature 1991; 354: 389-92.
3. Leanderson T, Kallberg E, Gray D. Expansion, selection and mutation of antigen-specific B cells in germinal centers. Immunol. Rev. 1992; 126: 47-61.
4. Jacob J, 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. 1992; 176: 679-87.
5. Jacob J, Przylepa J, Miller C, Kelsoe G. 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. 1993; 178: 1293-307.
6. Allen D, Simon T, Sablitzky F, Rajewsky K, Cumano A. Antibody engineering for the analysis of affinity maturation of an anti-hapten response. EMBO J. 1988; 7: 1995-2001.
7. Smith DS, Creadon G, Jena PK, Portanova JP, Kotzin BL, Wysocki LJ. Di- and trinucleotide target preferences of somatic mutagenesis in normal and autoreactive B cells. J. Immunol. 1996; 156: 2642-52.
8. Both GW, Taylor L, Pollard JW, Steele EJ. Distribution of mutations around rearranged heavy-chain antibody variable-region genes. Mol. Cell. Biol. 1990; 10: 5187-96.
9. Rickert R, Clarke S. Low frequencies of somatic mutation in two expressed Vk genes: unequal distributions of mutation in 5′ and 3′ flanking regions. Int. Immunol. 1993; 5: 255-63.
10. Lebecque S, Gearhart PJ. Boundaries of somatic mutation in rearranged immunoglobulin genes: 5′ boundary is near the promoter, and 3′ boundary is ∼1 kb form V(D)J gene. J. Exp. Med. 1990; 172: 1717-27.
11. Weber JS, Berry J, Manser T, Claflin JL. Position of the rearranged Vk and its 5′ flanking sequences determines the location of somatic mutations in the Jk locus. J. Immunol. 1991; 146: 3652-5.
12. Weber JS, Berry J, Litwin S, Claflin JL. Somatic hypermutation of the JC intron is markedly reduced in unrearranged k and H alleles and is unevenly distributed in rearranged alleles. J. Immunol. 1991; 146: 3218-26.
13. Weber JS, Berry J, Manser T, Claflin JL. Mutations in Ig V(D)J genes are distributed asymmetrically and independently of the position of V(D)J. J. Immunol. 1994; 153: 3594-602.
14. Bye JM, Carter C, Cui Y et al. Germline variable region gene segment derivation of human monoclonal anti-Rh (D) antibodies. Evidence for affinity maturation by somatic hypermutation and repertoire shift. J. Clin. Invest. 1992; 90: 2481-90.
15. Zhang J, MacLennan I, Liu YJ, Lane P. Is rapid proliferation in B centroblasts linked to somatic mutation in memory B cell clones? Immunol. Lett. 1988; 18: 297-9.
16. MacLennan ICM. Germinal centers. Annu. Rev. Immunol. 1994; 12: 117-39.
17. Hollowood K, McCartney J. Cell kinetics of the germinal center reaction a stathmokinetic study. Eur. J. Immunol. 1992; 22: 261-6.
18. McKean D, Huppi K, Bell M, Staudt L, Gerhard W, Weigert M. Generation of antibody diversity in the immune response of BALB/c mice to influenza virus hemagglutinin. Proc. Natl Acad. Sci. USA. 1984; 81: 3180-4.
19. Clarke SH, Huppi K, Ruezinsky D, Staudt L, Gerhard W, Weigert M. Inter- and intraclonal diversity in the antibody response to influenza hemagglutinin. J. Exp. Med. 1985; 161: 687-704.
20. McHeyzer-Williams MG, McLean MJ, Lalor PA, Nossal GJV. Antigen-driven B cell differentiation in vivo. J. Exp. Med. 1993; 178: 295-307.
21. Weiss U, Zoebelein R, Rajewsky K. Accumulation of somatic mutants in the B cell compartment after primary immunization with a T cell-dependent antigen. Eur. J. Immunol. 1992; 22: 511-17.
22. Nossal GJV. Differentiation of the secondary B-lymphocyte repertoire: The germinal center reaction. Immunol. Rev. 1994; 137: 173-83.
23. Jacob J, Kassir R, Kelsoe G. In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acelyl. I. The architecture and dynamics of responding cell populations. J. Exp. Med. 1991; 173: 1165-75.
24. Nieuwenhuis P, Opstelten D. Functional anatomy of germinal centers. Am. J. Anat. 1984; 170: 421-35.
25. Kroese FGM, Wubbena AS, Seijen HG, Nieuwenhuis P. Germinal centers develop oligoclonally. Eur. J. Immunol. 1987; 17: 1069-72.
26. 125I-labeled antigen in germinal centers of mouse spleen: Histologic and ultrastructural autoradiographic studies of the secondary immune reaction. J. Immunol. 1968; 101: 949-62.
27. Tew JG, Phipps RP, Mandel TE. The maintenance and regulation of the humoral immune response: Persisting antigen and the role of follicular antigen-binding dendritic cells as accessory cells. Immunol. Rev. 1980; 53: 175-201.
28. Smith KGC, Nossal GJV, Tarlinton DM. FAS is highly expressed in the germinal center hut is not required for regulation of the B-cell response to antigen. Proc. Natl Acad. Sci. USA. 1995; 92: 11 628-32.
29. MacLennan ICM, Liu Y, Oldfield S, Zhang J, Lane PJL. The evolution of B cell clones. Curr. Top. Microbiol. Immunol. 1990; 159: 37-63.
30. Han S, Hathcock K, Zheng B, Kepler T, Hodes R, Kelsoe G. Cellular interactions in germinal centers: Roles of CD40 ligand and B7-2 in established germinal centers. J. Immunol. 1995; 155: 556-67.
31. Jacobson E, Caporale L, Thorbecke G. Effect of thymus cell injections on germinal center formation in lymphoid tissues of nutle (thymusless) mice. Cell. Immunol. 1974; 13: 416-30.
32. Liu YJ, Joshua DE, Williams GT, Smith CA, Gordon J, MacLennan ICM. Mechanism of antigen-driven selection in germinal centres. Nature 1989; 342: 929-31.
33. Banchereau J, de Paoli P, Valle A, Garcia E, Roussel F. Long-term human B cell lines dependent on interleukin-4 and antibody to CD40. Science 1991; 251: 70-2.
34. Fuller KA, Kanagawa O, Nahm MH. T cells within germinal centers are specific for the immunizing antigen. J. Immunol. 1993; 151: 4505-12.
35. Kelsoe G, Zheng B. Sites of B cell activation in vivo. Curr. Opin. Immunol. 1993; 5: 418-22.
36. Smith KGC, Light A, Nossal GJV, Tarlinton DM. The extent of affinity maturation differs between the memory and antibody-forming cell compartments in the primary immune response. EMBO J. 1997; 16: 2996-3006.
37. Berek C, Milstein C. Mutation drift and repertoire shift in the maturation of the immune response. Immunol. Rev. 1987; 96: 23-41.
38. Cumano A, Rajewsky K. Clonal recruitment and somatic mutation in the generation of immunological memory to the hapten NP. EMBO J. 1986; 5: 2459-68.
39. Blier PR, Bothwell A. A limited number of B cell lineages generates the heterogeneity of a secondary immune response. J. Immunol. 1987; 139: 3996-4006.
40. Weiss U, Rajewsky K. The repertoire of somatic antibody mutants accumulating in the memory compartment after primary immunization is restricted through affinity maturation and mirrors that expressed in the secondary response. J. Exp. Med. 1990; 172: 1681-9.
41. Eisen H, Siskind GW. Variations in affinities of antibodies during the immune response. Biochem. 1964; 3: 996-1008.
42. Gray D, Skarvall H. Memory B cells are short-lived in the absence of antigen. Nature 1988; 336: 70-3.
43. Press W, Teukolsky S, Vetterling W, Flannery B. Numerical Recipes in FORTRAN. New York: Cambridge University Press, 1992.