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PMID: 10852106 Published · ppublish English Journal Article Review

Relative roles of somatic and Darwinian evolution in shaping the antibody response.

Immunologic research ·Vol. 21 ·No. 2-3 ·2000-00-00 ·Pages 89-102

Diaz M, Klinman NR

Abstract

The need for a highly specific system of recognition in immunity has resulted in the evolution of several somatic mechanisms such as V(D)J recombination, to diversify the repertoire of B cells. Therefore, repertoire diversification is the driving force for the cells that constitute the bulk of the response to unpredictable pathogens, the B2 naive B cells. Predictability of antigen, on the other hand, has played a major role in shaping the neonatal repertoire, in which evolution to recognize commonly encountered pathogens has driven the germline sequence of several VH segments that are used frequently in the neonatal repertoire. A third population, the memory B cell population, is generated to respond to a known pathogen, but predictability of the pathogen is not acquired until after a first exposure. Therefore, it is somatic evolution in germinal centers that drives the generation of high-affinity memory B cells.

MeSH Terms
Animals Antibody Formation/genetics B-Lymphocytes/immunology Biological Evolution Gene Rearrangement, B-Lymphocyte Genes, Immunoglobulin Humans Immunoglobulin Variable Region/genetics Recombination, Genetic
Chemicals
Immunoglobulin Variable Region
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Diaz M
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Klinman N R
References (65)
65 references, click to expand
  1. Increased hypermutation at G and C nucleotides in immunoglobulin variable genes from mice deficient in the MSH2 mismatch repair protein.
    J Exp Med. 1998 Jun 1;187(11):1745-51 PMID: 9607916
  2. Functions of the MDM2 oncoprotein.
    Cell Mol Life Sci. 1999 Jan;55(1):96-107 PMID: 10065155
  3. Somatic hypermutation of immunoglobulin genes is linked to transcription initiation.
    Immunity. 1996 Jan;4(1):57-65 PMID: 8574852
  4. Positive and negative selection events during B lymphopoiesis.
    Curr Opin Immunol. 1995 Apr;7(2):214-27 PMID: 7546381
  5. Fixing mismatches.
    Science. 1998 Feb 20;279(5354):1159-60 PMID: 9508690
  6. Evolution of somatic hypermutation and gene conversion in adaptive immunity.
    Immunol Rev. 1998 Apr;162:13-24 PMID: 9602348
  7. p53 mediates apoptosis induced by c-Myc activation in hypoxic or gamma irradiated fibroblasts.
    Cell Death Differ. 1998 Feb;5(2):141-7 PMID: 10200458
  8. Increased junctional diversity in fetal B cells results in a loss of protective anti-phosphorylcholine antibodies in adult mice.
    Immunity. 1999 May;10(5):607-17 PMID: 10367906
  9. Peripheral B cell maturation. II. Heat-stable antigen(hi) splenic B cells are an immature developmental intermediate in the production of long-lived marrow-derived B cells.
    J Immunol. 1993 Nov 1;151(9):4431-44 PMID: 8409411
  10. Tolerance susceptibility of newly generating memory B cells.
    J Immunol. 1991 Jun 15;146(12):4099-104 PMID: 2040792
  11. Defining subsets of naive and memory B cells based on the ability of their progeny to somatically mutate in vitro.
    Immunity. 1995 Feb;2(2):195-203 PMID: 7534621
  12. B lymphocytes may escape tolerance by revising their antigen receptors.
    J Exp Med. 1993 Apr 1;177(4):1165-73 PMID: 8459210
  13. Surrogate light chain-dependent selection of Ig heavy chain V regions.
    J Immunol. 1995 Dec 15;155(12):5536-42 PMID: 7499835
  14. The surrogate light chain in B-cell development.
    Immunol Today. 1993 Feb;14(2):60-8 PMID: 8166770
  15. Inhibition of immunoglobulin gene rearrangement by the expression of a lambda 2 transgene.
    J Exp Med. 1989 Jun 1;169(6):1911-29 PMID: 2499652
  16. Receptor editing and commitment in B lymphocytes.
    Curr Opin Immunol. 1998 Apr;10(2):208-13 PMID: 9602310
  17. Comparative expression of adult and fetal V gene repertoires.
    Int Rev Immunol. 1992;8(2-3):95-111 PMID: 1602218
  18. Mismatch repair and immunoglobulin gene hypermutation: did we learn something?
    Immunol Today. 1999 Nov;20(11):522-7 PMID: 10529781
  19. Genetic relatedness of human DNA polymerase beta and terminal deoxynucleotidyltransferase.
    Gene. 1987;60(2-3):163-73 PMID: 3443300
  20. The cellular origins of memory B cells.
    Semin Immunol. 1997 Aug;9(4):241-7 PMID: 9237930
  21. The mannose receptor is a pattern recognition receptor involved in host defense.
    Curr Opin Immunol. 1998 Feb;10(1):50-5 PMID: 9523111
  22. The somatic generation of immune recognition.
    Eur J Immunol. 1971 Jan;1(1):1-9 PMID: 14978855
  23. Human germinal center B cells express the apoptosis-inducing genes Fas, c-myc, P53, and Bax but not the survival gene bcl-2.
    J Exp Med. 1996 Mar 1;183(3):971-7 PMID: 8642300
  24. Origin of murine B cell lineages.
    Annu Rev Immunol. 1993;11:501-38 PMID: 8476571
  25. Insertion of N regions into heavy-chain genes is correlated with expression of terminal deoxytransferase in B cells.
    Nature. 1984 Oct 25-31;311(5988):752-5 PMID: 6092963
  26. Mutational pattern of the nurse shark antigen receptor gene (NAR) is similar to that of mammalian Ig genes and to spontaneous mutations in evolution: the translesion synthesis model of somatic hypermutation.
    Int Immunol. 1999 May;11(5):825-33 PMID: 10330287
  27. The mutagenesis proteins UmuD' and UmuC prevent lethal frameshifts while increasing base substitution mutations.
    Mol Cell. 1998 Aug;2(2):191-9 PMID: 9734356
  28. B cell maintenance in aged mice reflects both increased B cell longevity and decreased B cell generation.
    J Immunol. 1999 Mar 15;162(6):3342-9 PMID: 10092788
  29. Pre-B cell receptor-mediated selection of pre-B cells synthesizing functional mu heavy chains.
    J Immunol. 1998 Aug 15;161(4):1608-18 PMID: 9712022
  30. Lack of N regions in fetal and neonatal mouse immunoglobulin V-D-J junctional sequences.
    J Exp Med. 1990 Nov 1;172(5):1377-90 PMID: 1700054
  31. The generation of B-cell memory: a working hypothesis.
    Curr Top Microbiol Immunol. 1990;159:19-35 PMID: 2189691
  32. Somatic generation of antibody diversity.
    Nature. 1983 Apr 14;302(5909):575-81 PMID: 6300689
  33. Receptor editing occurs frequently during normal B cell development.
    J Exp Med. 1998 Oct 5;188(7):1231-8 PMID: 9763602
  34. Heavy chain V gene-specific elimination of B cells during the pre-B cell to B cell transition.
    J Immunol. 1995 May 15;154(10):4924-35 PMID: 7730605
  35. Germinal center founder cells display propensity for apoptosis before onset of somatic mutation.
    J Exp Med. 1997 Feb 3;185(3):563-71 PMID: 9053456
  36. A novel mechanism for B cell repertoire maturation based on response by B cell precursors to pre-B receptor assembly.
    J Exp Med. 1998 Jan 19;187(2):259-64 PMID: 9432984
  37. Primary antibody-forming cells and secondary B cells are generated from separate precursor cell subpopulations.
    Cell. 1989 Dec 22;59(6):1049-59 PMID: 2598260
  38. Molecular mechanisms governing reading frame choice of immunoglobulin diversity genes.
    Immunol Today. 1997 Jan;18(1):37-43 PMID: 9018973
  39. The role of components of recombination signal sequences in immunoglobulin gene segment usage: a V81x model.
    Nucleic Acids Res. 1999 Jun 1;27(11):2304-9 PMID: 10325418
  40. Biased expression of JH-proximal VH genes occurs in the newly generated repertoire of neonatal and adult mice.
    J Exp Med. 1990 Mar 1;171(3):843-59 PMID: 2261012
  41. A new antigen receptor gene family that undergoes rearrangement and extensive somatic diversification in sharks.
    Nature. 1995 Mar 9;374(6518):168-73 PMID: 7877689
  42. Lambda 5, a new light-chain-related locus selectively expressed in pre-B lymphocytes.
    Nature. 1986 Dec 11-17;324(6097):579-82 PMID: 3024017
  43. Reading of D genes in variable frames as a source of antibody diversity.
    Immunol Today. 1985 Nov;6(11):324-7 PMID: 25291001
  44. Allelic exclusion in transgenic mice that express the membrane form of immunoglobulin mu.
    Science. 1987 May 15;236(4803):816-9 PMID: 3107126
  45. Sequence homologies, N sequence insertion and JH gene utilization in VHDJH joining: implications for the joining mechanism and the ontogenetic timing of Ly1 B cell and B-CLL progenitor generation.
    EMBO J. 1990 Jul;9(7):2133-40 PMID: 2113468
  46. Relationship of germinal centers in lymphoid tissue to immunologic memory. VI. Transfer of B cell memory with lymph node cells fractionated according to their receptors for peanut agglutinin.
    J Immunol. 1983 Nov;131(5):2254-7 PMID: 6605381
  47. Diversity of Ig light chain clusters in the sandbar shark (Carcharhinus plumbeus).
    J Immunol. 1995 Oct 15;155(8):3922-8 PMID: 7561099
  48. Predominance of nonproductive rearrangements of VH81X gene segments evidences a dependence of B cell clonal maturation on the structure of nascent H chains.
    J Immunol. 1991 Aug 15;147(4):1406-11 PMID: 1907997
  49. Targeted disruption of the MYC antagonist MAD1 inhibits cell cycle exit during granulocyte differentiation.
    EMBO J. 1998 Feb 2;17(3):774-85 PMID: 9451002
  50. The characterization fo the B-cell repertoire specific for the 2,4-dinitrophenyl and 2,4,6-trinitrophenyl determinants in neonatal BALB/c mice.
    J Exp Med. 1975 May 1;141(5):1133-46 PMID: 47895
  51. In vitro tolerance induction of bone marrow cells: a marker for B cell maturation.
    J Immunol. 1977 Jun;118(6):2111-6 PMID: 405423
  52. The CDR1 sequences of a major proportion of human germline Ig VH genes are inherently susceptible to amino acid replacement.
    Immunol Today. 1994 Aug;15(8):367-73 PMID: 7916950
  53. Somatic hypermutation of the new antigen receptor gene (NAR) in the nurse shark does not generate the repertoire: possible role in antigen-driven reactions in the absence of germinal centers.
    Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14343-8 PMID: 9826702
  54. C3d of complement as a molecular adjuvant: bridging innate and acquired immunity.
    Science. 1996 Jan 19;271(5247):348-50 PMID: 8553069
  55. Predominance of VH-D-JH junctions occurring at sites of short sequence homology results in limited junctional diversity in neonatal antibodies.
    J Immunol. 1992 Jul 1;149(1):222-9 PMID: 1607655
  56. The expression of the Ig H chain repertoire in developing bone marrow B lineage cells.
    J Immunol. 1991 Jan 1;146(1):350-61 PMID: 1898607
  57. Expression of immunoglobulin delta chain causes allelic exclusion in transgenic mice.
    Nature. 1987 Dec 3-9;330(6147):482-4 PMID: 3120014
  58. Rearrangements of DNA mediated by terminal transferase.
    Proc Natl Acad Sci U S A. 1986 Mar;83(6):1867-71 PMID: 2937062
  59. The dynamic structure of the germinal center.
    Immunol Today. 1998 Nov;19(11):511-4 PMID: 9818545
  60. 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. 1995 Dec 1;182(6):1635-44 PMID: 7500008
  61. The joining of V and J gene segments creates antibody diversity.
    Nature. 1980 Jan 31;283(5746):497-9 PMID: 6766210
  62. A hyperconversion mechanism generates the chicken light chain preimmune repertoire.
    Cell. 1987 Feb 13;48(3):379-88 PMID: 3100050
  63. Somatic variation precedes extensive diversification of germline sequences and combinatorial joining in the evolution of immunoglobulin heavy chain diversity.
    J Exp Med. 1993 Sep 1;178(3):815-24 PMID: 8350055
  64. 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 Sep 1;176(3):679-87 PMID: 1512536
  65. Hypermutation generating the sheep immunoglobulin repertoire is an antigen-independent process.
    Cell. 1995 Jan 13;80(1):115-25 PMID: 7813007
Article Info
Journal
Immunologic research
Abbr.
Immunol Res
ISSN
0257-277X
DOI
10.1385/IR:21:2-3:89
Published
2000-00-00
Pages
89-102
Language
English
Region
United States
NLM ID
8611087
Subset
IM
External Links
PubMed source DOI: 10.1385/IR:21:2-3:89 View journal details
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