Development of the immunoglobulin repertoire

Clinical Immunology and Immunopathology

Volumn 79, Issue 1, 1996, Pages 1-14

  Fanning, Liam J ^a   Connor, Alison M ^a   Wu, Gillian E ^a  

^a UNIVERSITY OF TORONTO   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

AUTOANTIBODY; IMMUNOGLOBULIN;

AUTOIMMUNITY; B LYMPHOCYTE; ETIOLOGY; HUMAN; HUMAN CELL; IMMUNE SYSTEM; PRIORITY JOURNAL; REVIEW;

EID: 0029877768     PISSN: 00901229     EISSN: None     Source Type: Journal    
DOI: 10.1006/clin.1996.0044     Document Type: Review

References (129)

1. Mombaerts, P., Iacomini, J., Johnson, R. S., Herrup, K., Tonegawa, S., and Papioannou, V. E., RAG-1-deficient mice have no mature B and T lymphocytes. Cell 68, 869-877, 1992.
2. Oettinger, M. A., Schatz, D. G., Gorka, C., and Baltimore, D., RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination. Science 248, 1517-1523, 1990.
3. Schatz, D. G., Oettinger, M. A., and Schlissel, M. S., V(D)J recombination: Molecular biology and regulation. Annu. Rev. Immunol. 10, 359-383, 1992.
4. Alt, F. W., Rathbun, G., Oltz, E., Taccioli, G., and Shinkai, Y., Function and control of recombination-activating gene activity: Review. Ann. N. Y. Acad. Sci. 651, 277-294, 1992.
5. Shinkai, Y., Koyasu, S., Nakayama, K., Murphy, K. M., Loh, D. Y., Reinherz, E. L., and Alt, F. W., Restoration of T cell development in RAG-2-deficient mice by functional TCR transgenes. Science 259, 822-825, 1993.
6. van Gent, D. C., Fraser, J., McBlane, J. F., Ramsden, D. A., Sadofsky, M. J., Hesse, J. E., and, Gellert M., Initiation of V(D)J recombination in a cell free system. Cell 81, 925-934, 1995.
7. Lieber, M. R., The mechanism of V(D)J recombination: A balance of diveristy, specificity, and stability. Cell 70, 873-876, 1992.
8. Cumano, A., Kee, B. L., Ramsden, D. A., Marshall, A., Paige, C. J., and Wu, G. E., Development of B lymphocytes from lymphoid committed and uncommitted progenitors. Immunol. Rev. 137, 5-23, 1994.
9. Lewis, S., The mechanisms of V(D)J joining: Lessons from molecular, immunological and comparative analyses. Adv. Immunol. 56, 27-150, 1994.
10. Tonegawa, S., Somatic generation of antibody diversity. Nature 302, 575-581, 1983.
11. Kurosawa, Y., and , Tonegawa S., Organization, structure and assembly of immunoglobulin heavy chain diversity DNA segments. J. Exp. Med 155, 201-218, 1982.
12. Brodeur, P., Thompson, M., and Riblet, R., The content and organization of the mouse IgH-V families In "Regulation of the Immune System" (H. Cantor, L. Chess, and E. Sercarz, Eds), pp. 445-453, A. R. Liss, New York, 1984.
13. Christoph, T., and Krawinkel, U., Physical linkage of variable, diversity and joining gene segments in the immunoglobulin heavy chain locus of the mouse. Eur. J. Immunol. 19, 1521-1523, 1989.
14. Berman, J. E., Mellis, S. J., Pollock, R., Smith, C. L., Suh, H., Heinke, B., Kowal, C., Surti, U., Chess, L., Cantor, C. R., and Alt, F. W., Content and organization of the human IgVH locus: Definition of three new families and linkage to the IgCH locus. EMBO J. 7, 727-738, 1988.
15. Sakano, H., Maki, R., Kurosawa, Y., Roeder, W., and Tonegawa, S., Two types of somatic recombination are necessary for the generation of complete immunoglobulin heavy chain genes. Nature 286, 676-683, 1980.
16. Sakano, H., Kurosawa, Y., Weigert, M., and Tonegawa, S., Identification and nucleotide sequence of a diversity DNA segment (D) of immunoglobulin heavy-chain genes. Nature 290, 562-565, 1981.
17. Rajewsky, K., Förster, I., and Cumano, A., Evolution and somatic selection of the antibody repertoire in the mouse. Science 238, 1088-1094, 1987.
18. Berek, C., and Milstein, C., The dynamic nature of the antibody repertoire: Review. Immunol. Rev. 105, 5-26, 1988.
19. Kabat, E. A., Wu, T. T., Reid-Miller, M., Perry, H. M., and Gottesman, K. S., In "Sequences of Proteins of Immunological Interest." National Institutes of Health Publication 165-462, Bethesda, MD, 1987.
20. Schroeder, H. W., Jr., Mortari, F., Shiokawa, S., Kirkham, P. M., Elgavish, R. A., and Bertrand, F. E., III, Developmental regulation of the human antibody repertoire. Ann. N.Y. Acad. Sci., in press, 1995.
21. Brodeur, P., and Riblet, R., The immunoglobulin heavy chain variable region (Igh-V) locus in mouse: One hundred Igh-V genes comprise seven families of homologous genes. Eur. J. Immunol. 14, 922-933, 1984.
22. Ichihara, Y., Hayashida, H., Miyazawa, S., and Kurosawa, Y., Only DFL16, DSP2 and DQ52 gene families exist in mouse immunoglobulin heavy chain diversity gene loci, of which DFL16 and DSP2 originate from the same primordial DH gene. Eur. J. Immunol. 19, 1849-1854, 1989.
23. Gu, H., Kitamura, D., and Rajewsky, K., B cell development regulated by gene rearrangement: Arrest of maturation by membrane-bound Dm protein and selection of DH element reading frames. Cell 65, 47-54, 1991.
24. Gu, H., Förster, I, and Rajewsky, K., Sequence homologies, N sequence insertion and JH gene utilization in VHDJH joining: Implications for the joining mechanism and the ontogenic timing of Ly 1 B cell and B-CLL progenitor generation. EMBO J. 9, 2133-2140, 1990.
25. Chang, Y. H., Paige, C. J., and Wu, G. E., Enumeration and characterization of DJH rearrangements in fetal liver. EMBO J. 11, 1891-1899, 1992.
26. Pennycook, J. L., Chang, Y., Celler, J., Phillips, R. A., and Wu, G. E., High frequency of normal DJH joints in SCID mice. J. Exp. Med. 178, 1007-1016, 1993.
27. Reth, M., Gehrmann, P., Petrac, E., and Wiese, P., A novel VH to VHDJH joining mechanism in heavy-chain-negative (null) pre-B cells results in heavy chain production. Nature 322, 840-842, 1986.
28. Nickerson, K., Berman, J., Glickman, E., Chess, L., and Alt, F., Early human IgH gene assembly in Epstein-Barr virus transformed fetal B cell lines. J. Exp. Med. 169, 1391-1403, 1989.
29. Feeney, A. J., Lack of N regions in fetal and neonatal mouse immunoglobulin V-D-J junctional sequences. J. Exp. Med. 172, 1377-1390, 1990.
30. Tsukada, S., Sugiyama, H., Oka, Y., and Kishimoto, S., Estimation of D-segment usage in initial D to JH joinings in a murine immature B cell line: Preferential utilization of DFL16.1, the most 5′ D segment and DQ52, the most JH-proximal D segment. J. Immunol. 144, 4053-4059, 1990.
31. Rolink, A., Kudo, A., Karasuyama, H., Kikuchi, Y., and Melchers, F., Long term proliferating early pre B cell lines and clones with the potential to develop to surface Ig-positive, mitogen reactive B cells in vitro and in vivo. EMBO J. 10, 327-336, 1991.
32. Atkinson, M. J., Chang, Y. H., Celler, J., Huang, C., Paige, C. J., and Wu, G. E., Overusage of DFL16.1 is strain dependant and determined by cis-acting elements. Dev. Immunol. 3, 283-295, 1994.
33. Tao, W., and Bothwell, A. L., Development of B cell lineages during a primary anti-hapten immune response. J. Immunol. 145, 3216-3222, 1990.
34. Ravetch, J. V., Siebenlist, U., Korsmeyer, S., Waldmann, T., and Leder, P., Structure of the human immunoglobulin mu locus: Characterization of embryonic and rearranged J and D genes. Cell 27, 583-591, 1981.
35. Schroeder, H., Jr., and Wang, J. Y., Preferential utilization of conserved immunoglobulin heavy chain variable gene segments during human fetal life. Proc. Natl. Acad. Sci. USA 87, 6146-6150, 1990.
36. Deleted at proof.
37. Yamada, M., Wasserman, R., Reichard, B. A., Shane, S., Caton, A. J., and Rovera, G., Preferential utilization of specific immunoglobulin heavy chain diversity and joining segments in adult human peripheral blood B lymphocytes. J. Exp. Med. 173, 395-407, 1991.
38. Pascual, V., Verkruyse, L., Casey, M. L., and Capra, J. D., Analysis of Ig H chain gene segment utilization in human fetal liver: Revisiting the "proximal utilization hypothesis." J. Immunol. 151, 4164-4172, 1993.
39. Brodeur, P. H., Osman, G. E., Mackie, J. J., and Lalor, J. M., The organization of the mouse Igh-V locus: Dispersion, interspersion and the evolution of VH gene family clusters. J. Exp. Med. 168, 2261-2278, 1988.
40. Blankenstein, T, and Krawinkel, U., Immunoglobulin VH region genes in mice are arranged in overlapping clusters. Eur. J. Immunol. 17, 1351-1357, 1987.
41. Kleinfield, R., and Weigert, M., Analysis of VH gene replacement events in a B-cell lymphoma. J. Immunol. 142, 4483-4492, 1989.
42. Rathburn, G. A., Capra, J. D., and Tucker, P. W., Organization of the murine VH complex in the inbred strains. EMBO J. 6, 2931-2937, 1987.
43. Pascual, V., and Capra, J. D., Human immunoglobulin heavychain variable region genes: Organization, polymorphism, and expression (Review). Adv. Immunol. 49, 1-74, 1991.
44. Kodaira, M., Kinashi, T., Umemura, I., Matesude, F., Noma, T., Ono, Y., and Honjo, T., Organization and evolution of variable region genes of the human immunoglobulin heavy chain. J. Mol. Biol. 190, 529-541, 1986.
45. Hofker, M. H., Walter, M. A., and Cox, D. W., Complete physical map of the human immunoglobulin heavy chain constant region gene complex. Proc. Natl. Acad. Sci. USA 1989, 5567-5571, 1989.
46. Schroeder, H. W., Jr., Walter, M. A., Hofker, M. H., Ebens, A., Van Dijk, K. W., Liao, L. C., Cox, D. W., Milner, E.C. B., and Perlmutter, R. M., Physical linkage of a human immunoglobulin heavy chain variable region gene segment to diversity and joining region elements. Proc. Natl. Acad. Sci. USA 85, 8196-8200, 1988.
47. Deleted at proof.
48. Walter, M., Hofken, M., and Cox, D., The physical map of the human immunoglobulin heavy chain region. Am. J. Hum. Genet. 45, A166, 1989.
49. Walter, M., and Cox, D., The physical map of the human immunoglobulin heavy chain variable region. Genet. Soc. Can. Bull. 20, D15, 1989.
50. Walter, M. A., Surti, U., Hofker, M. H., and Cox, D. W., The physical organization of the human immunoglobulin heavy chain gene complex. EMBO J. 9, 3303-3313, 1990.
51. Newkirk, M., and Capra, J. D., Restricted usage of immunoglobulin variable region genes in human autoantibodies. In "Immunoglobulin Genes" (T. Honjo, F. Alt, and T. Rabbitts, Eds.), pp. 203-220, Academic Press, San Diego/London, 1989.
52. Livant, D., Blatt, C., and Hood, L., One heavy chain variable region gene segment subfamily in the BALB/c mouse contains 500-1000 or more members. Cell. 47, 461-470, 1986.
53. Carlsson, L., Övermo, C., and Holmberg, D., Developmentally controlled selection of antibody genes: Characterization of individual VH7183 genes and evidence for stage-specific somatic diversification. Eur. J. Immunol. 22, 71-78, 1992.
54. Atkinson, M. J., and Wu, G. E., Genomic sequence of a V(D)J rearrangement utilizing a new VH7183 family member VH183.15. Mol. Immunol. 30, 109-110, 1993.
55. Yancopoulos, G. D., Desiderio, S. V., Paskind, M., Kearney, J. F., Baltimore, D., and Alt, F. W., Preferential utilization of the most JH-proximal VH gene segments in pre-B-cell lines. Nature 311, 727-733, 1984.
56. Perlmutter, R. M., Kearney, J. F., Chang, S. P., and Hood, L. E., Developmentally controlled expression of immunoglobulin VH genes. Science 227, 1596-1601, 1985.
57. Lawler, A. M., Lin, P. S., and Gearhart, P. J., Adult B-cell repertoire is biased toward two heavy chain variable region genes that rearrange frequently in fetal pre-B cells. Proc. Natl. Acad. Sci. USA 84, 2454-2458, 1987.
58. Decker, D. J., Boyle, N. E., Koziol, J. A., and Klinman, N. R., The expression of the IgH repertoire in developing bone marrow B lineage cells. J. Immunol. 146, 350-361, 1991.
59. Huetz, F., Carlsson, L., Tornberg, U., and Holmberg, D., V-region directed selection in differentiating B lymphocytes. EMBO J. 12, 1819-1826, 1993.
60. Osman, G. E., Wortis, H. H., and Brodeur, P. H., Strain variation in the frequency of Abelson murine leukemia virus-transformed fetal liver pre-B cells bearing complete immunoglobulin heavy chain rearrangements. J. Exp. Med. 168, 2023-2030, 1988.
61. Sheehan, K. M., and Brodeur, P. H., Molecular cloning of the primary IgH repertoire: A quantitative analysis of VH gene usage in adult mice. EMBO J. 8, 2313-2320, 1989.
62. Freitas, A. A., Andrade, L., Lembezat, M.-P., and Coutinho, A., Selection of VH gene repertoires: Differentiating cells of adult bone marrow mimic fetal development. Int. Immunol. 2, 15-23, 1990.
63. Freitas, A. A., Lembezat, M. P., and Coutinho, A., Expression of antibody V-regions is genetically and developmentally controlled and modulated by the B lymphocyte environment. Int. Immunol. 1, 342-354, 1989.
64. Wu, G. E., and Paige, C. J., VH gene family utilization in colonies from B and pre-B cells detected by the RNA colony blot assay. EMBO J. 5, 3475-3481, 1986.
65. Dildrop, R., Krawinkel, U., Winter, E., and Rajewsky, K., VH gene expression in murine lipopolysaccharide blasts distributes over the nine known VH gene groups and may be random. Eur. J. Immunol. 15, 1154-1156, 1985.
66. Holmberg, D., Freitas, A. A., Portnoi, D., Jacquemart, F., Avrameas, S., and Coutinho, A., Antibody repertoires of normal BALB/c mice: B lymphocyte populations denned by state of activation. Immunol. Rev. 93, 147-169, 1986.
67. Jeong, H. D., Komisar, J. L., Kraig, E., and Teale, J. M., Strain dependant expression of VH gene families. J. Immunol. 140, 2436-2441, 1988.
68. Jeong, H. D., and Teale, J. L., Comparison of fetal and adult functional B cell repertoires by analysis of VH gene family expression. J. Exp. Med. 168, 589-603, 1988.
69. Wu, G. E., Atkinson, M., Ramsden, D., and Paige, C. J., VH gene repertoire. Semin. Immunol. 2, 207-216, 1990.
70. Cuisinier, A. M., Fumoux, F., Moinier, D., Boubli, L., Guigou, V., Milili, M., Schiff, C., Fougereau, M., and Tonnelle, C., Rapid expansion of human immunoglobulin repertoire (VH, V kappa, V lambda) expressed in early fetal bone marrow. New Biologist 2, 689-699, 1990.
71. Schroeder, H., Jr., Hillson, J., and Permutter, R., Early restriction of the human antibody repertoire. Science 238, 791-793, 1987.
72. Raaphorst, F. M., Timmers, E., Kenter, M. J. H., Van Tol, M. J. D., Vossen, J. M., and Schuurman, R. K. B., Restricted utilization of germline VH3 genes and short diverse third complementarity-determining regions (CDR3) in human fetal B lymphocyte immunoglobulin heavy chain rearrangements. Eur. J. Immunol. 22, 247-251, 1992.
73. Kofler, R., Duchosal, M. A., and Dixon, F. J., Complexity, polymorphism, and connectivity of mouse VA gene families. Immunogenetics 29, 65-74, 1989.
74. Lewis, S., Rosenberg, N., Alt, F., and Baltimore, D., Continuing kappa-gene rearrangement in a cell line transformed by Abelson murine leukemia virus. Cell. 30, 807-816, 1982.
75. + B cells can continue to rearrange k and 1L chain gene loci. J. Exp. Med. 178, 1263-1270, 1993.
76. Medina, C. A., and Teale, J. M., Restricted kappa chain expression in early ontogeny: Biased utilization of V kappa exons and preferential V kappa-J kappa recombinations. J. Exp. Med. 177, 1317-1330, 1993.
77. Kalled, S. L., and Brodeur, P. H., Preferential rearrangement of Vk4 gene segments in pre-B cell lines. J. Exp. Med. 172, 559-566, 1990.
78. Ramsden, D. A., Paige, C. J., and Wu, G. E., k light chain rearrangement in mouse fetal liver. J. Immunol. 153, 1150-1160, 1994.
79. Kalled, S. L., and Brodeur, P. H., Utilization of Vk families and Vk exons: Implications for the available B cell repertoire. J. Immunol. 147, 3194-3200, 1991.
80. Tan, E. M., Autoantibodies to nuclear antigens (ANA): Their immunobiology and medicine (Review). Adv. Immunol. 33, 167-240, 1982.
81. Siminovitch, K. A., Misener, V., Kwong, P. C., Song, Q. L., and Chen, P. P., A natural autoantibody is encoded by germline heavy and lambda light chain variable region genes without somatic mutation. J. Clin. Invest. 84, 1675-1678, 1989.
82. Hahn, B. H., Characteristics of pathogenic subpopulations of antibodies to DNA. Arthritis Rheum. 25, 747-752, 1982.
83. Tsao, B. P., Ebling, F. M., Roman, C., Panosian, S. N., Calame, K., and Hahn, B. H., Structural characteristics of the variable regions of immunoglobulin genes encoding a pathogenic autoantibody in murine lupus. J. Clin. Invest. 85, 530-540, 1990.
84. Zouali, M., Chastagner, P., Abadie, A., and Theze, J., Organization of the immunoglobulin heavy chain variable region gene complex in human lupus. Immunogenetics 32, 451-455, 1990.
85. Stewart, A. K., Huang, C., Long, A. A., Stollar, B. D., and Schwartz, R. S., VH-gene representation in autoantibodies reflects the normal human B-cell repertoire. Immunol. Rev. 128, 101-122, 1992.
86. Stewart, A. K., Huang, C., Stollar, B. D., and Schwartz, R. S., High-frequency representation of a single VH gene in the expressed human B cell repertoire. J. Immunol. 177, 1227-1233, 1993.
87. Huang, C., and Stollar, B. D., A majority of Ig H chain cDNA of normal human adult blood lymphocytes resembles cDNA for fetal Ig and natural autoantibodies. J. Immunol. 151, 5290-5300, 1993.
88. Trepicchio, W. J., Maruya, A., and Barrett, K. J., The heavy chain genes of a lupus anti-DNA autoantibody are encoded in the germ line of a nonautoimmune strain of mouse and conserved in strains of mice polymorphic for this gene locus. J. Immunol. 139, 3139-3145, 1987.
89. Gangemi, R. M., Singh, A. K., and Barrett, K. J., Independently derived IgG anti-DNA autoantibodies from two lupus-prone mouse strains express a VH gene that is not present in most murine strains. J. Immunol. 151, 4660-4671, 1993.
90. Bensimon, C., Chastagner, P., and Zouali, M., Human lupus anti-DNA autoantibodies undergo essentially primary V kappa gene rearrangements. EMBO J. 13, 2951-2962, 1994.
91. Hozumi, N., and Tonegawa, S., Evidence for somatic rearrangement of immunoglobulin genes coding for variable and constant regions. Proc. Natl. Acad. Sci. USA 73, 3628-3632, 1976.
92. Early, P., Huang, M., Calame, K., and Hood, L., An immunoglobulin heavy chain variable region gene is generated from three segments of DNA: VH, D and JH. Cell 19, 981-992, 1980.
93. Akira, S., Okazaki, K., and Sakano, H., Two pairs of recombination signals are sufficient to cause immunoglobulin V-(D)-J joining. Science 238, 1134-1138, 1987.
94. Gellert, M., Molecular analysis of V(D)J recombination. Annu. Rev. Genet. 22, 425-446, 1992.
95. Connor, A., Fanning, L., Celler, J., Hicks, L., Ramsden, D., and Wu, G. E., Mouse VH7183 recombination signal sequences mediate recombination more frequently than do those of VHJ5581. J. Immunol., in press, 1995.
96. Suzuki, H., and Shiko, H., Preferential usage of JH2 in D-J joinings with DQ52 is determined by the primary DNA sequence and is largely dependent on recombination signal sequences. Eur. J. Immunol. 22, 2225-2230, 1992.
97. Ramsden, D. A., and Wu, G. E., Mouse k light-chain recombination signal sequences mediate recombination more frequently than those of 1 light chain. Proc. Natl. Acad. Sci. USA 88, 10721-10725, 1991.
98. Ramsden, D. A., Baetz, K., and Wu, G. E., Conservation and functional significance of the V(D)J recombination signal sequences. Nucleic Acids Res. 22, 1785-1796, 1994.
99. Wei, Z., and Lieber, M., Lymphoid V(D)J recombination: Functional analysis of the spacer sequence within the recombination signal. J. Biol. Chem. 268, 3180-3183, 1993.
100. Hesse, J., Lieber, M., Mizzuuchi, K., and Gellert, M., V(D)J recombination: A functional definition of the joining signals. Genes Dev. 3, 1953-1961, 1989.
101. Lieber, M. R., Hesse, J. E., Mizuuchi, K., and Gellert, M., Developmental stage specificity of the lymphoid V(D)J recombination activity. Genes Dev. 1, 751-761, 1987.
102. Hsieh, C., and Lieber, M., CpG methylated minichromosomes become inaccessible for V(D)J recombination after undergoing replication. EMBO J. 11, 315-325, 1992.
103. Hsieh, C., McCloskey, R. P., and Lieber, M., V(D)J recombination on minichromosomes is not affected by transcription. J. Biol. Chem. 267, 15613-15619, 1992.
104. Hsieh, C., McCloskey, R. P., Radany, E., and Lieber, M., V(D)J recombination: Evidence that a replicative mechanism is not required. Mol. Cell. Biol. 11, 3972-3977, 1991.
105. Gerstein, R. M., and Lieber, M. R., Extent to which homology can constrain coding exon junctional diversity in V(D)J recombination. Nature 363, 625-627, 1993.
106. Chen, P. P., Structural analysis of human developmentally regulated Vh3 genes. Scand. J. Immunol. 31, 257-267, 1990.
107. Chen, P. P., Soto, G. R., and Carson, D. A., The early expression of some human autoantibody-associated heavy chain variable region genes is controlled by specific regulatory elements: Review. Scand. J. Immunol. 31, 673-678, 1990.
108. Martin, D. J., and Van Ness, B. G., Initiation and processing of two kappa immunoglobulin germline transcripts in mouse B cells. Mol. Cell. Biol. 10, 1950-58, 1990.
109. Kottmann, A. H., Brack, C., Eibel, H., and Kohler, G., A survey of protein-DNA interaction sites within the murine immunoglobulin heavy chain locus reveals a particularly complex pattern around the DQ52 element. Eur. J. Immunol. 22, 2113-2120, 1992.
110. Thompson, A., Timmers, E., Schuurman, R. K. B., and Hendriks, R. W., Immunoglobulin heavy chain germ-line Jh-Cu transcription in human precursor B lymphocytes initiates in a unique region upstream of DQ52. Eur. J. Immunol. 25, 257-261, 1995.
111. Thompson, A., Timmers, E., Schuurman, K. B., and Hendriks, R. W., Immunoglobulin heavy chain germ-line JH-Cm transcription in human precursor B lymphocytes initiates in a unique region upstream of DQ52. Eur. J. Immunol. 25, 257-261, 1995.
112. Pennycook, J. L., Marshall, A., and Wu, G. E., PCR assays for endogenous V(D)J rearrangement. In "Immunological Methods Manual." Academic Press, San Diego/London, in press, 1995.
113. Meek, K., Analysis of junctional diversity during B lymphocyte development. Science. 250, 820-823, 1990.
114. Feeney, A. J., Predominance of VH-D-JH junctions occurring at sites of short sequence homology results in limited junctional diversity in neonatal antibodies. J. Immunol. 149, 222-229, 1992.
115. Chukwuocha, R. U., Nadel, B., and Feeney, A. J., Analysis of homology-directed recombination in VDJ junctions from cytoplasmic Ig- pre-B cells of newborn mice. J. Immunol. 154, 1246-1255, 1995.
116. Gauss, H., Lieber, M., The basis for the mechanistic bias for deletional over inversional V(D)J recombination. Genes Dev. 6, 1553-1561, 1992.
117. Gallo, M. L., Pergola, F., Daniels, G. A., and Lieber, M. R., Distinct roles for Rag-1 in the initiation of V(D)J recombination and in the resolution of coding ends. J. Biol. Chem. 269, 22188-22192, 1994.
118. Sadofsky, M. J., Hesse, J. E., and Gellert, M., Definition of a core region of RAG-2 that is functional in V(D)J recombination. Nucleic Acids Res. 22, 1805-1809, 1994.
119. Sadofsky, M. J., Hesse, J. E., McBlane, J. F., and Gellert, M., Expression and V(D)J recombination activity of mutated RAG-1 proteins. Nucleic Acids Res. 21, 5644-5650, 1993; Erratum appears in Nucleic Acids Res. 22(3), 550, 1994.
120. Cuomo, C. A., and Oettinger, M. A., Analysis of regions of RAG-2 important for V(D)J recombination. Nucleic Acids Res. 22, 1810-1814, 1994.
121. Ezekiel, U. R., Engler, P., Stern, D., and Storb, U., Asymmetric processing of coding ends and the effect of coding end nucleotide composition on V(D)J recombination. Immunity 2, 381-391, 1995.
122. Chen, C., Nagy, Z., Radic, M. Z., Hardy, R. R., Huszar, D., Camper, S. A., and Welgert, M., The site and stage of anti-DNA B-cell deletion. Nature 373, 252-255, 1995.
123. Russell, D. M., Dembić, Z., Morahan, G., Miller, J. F. A. P., Bürki, K., and Nemazee, D., Peripheral deletion of self-reactive B cells. Nature 354, 308-311, 1991.
124. Buhlmann, J. E., Foy, T. M., Arufflo, A., Crassi, K. M., Ledbetter, J. A., Green, W. R., Xu, J. C., Shultz, W. R., Roopesian, D., Flavell, R. A., Fast, L., Noelle, R. J., and Durie, F. H., In the absence of a CD40 signal B cells are tolerogenic. Immunity 2, 645-653, 1995.
125. Tiegs, S. L., Russell, D. M., and Nemazee, D., Receptor editing in self-reactive bone marrow B cells. J. Exp. Med. 177, 1009-1020, 1993.
126. Kalled, S. L., and Brodeur, P. H., Utilization of V kappa families and V kappa exons. Implications for the available B cell repertoire. J. Immunol. 147, 3194-3200, 1991.
127. Harada, K., and Yamagishi, H., Lack of feedback inhibition of Vk gene rearrangement by productively rearranded alleles. J. Exp. Med. 173, 409-415, 1991.
128. Luning Prak, E., Trounstine, M., Huszar, D., and Weigert, M., Light chain editing in k-deficient animals: A potential mechanism of B cell tolerance. J. Exp. Med. 180, 1805-1815, 1994.
129. Radic, M., Erikson, J., Litwin, S., and Weigert, M., B lymphocytes may escape tolerance by revising their antigen receptors. J. Exp. Med. 177, 1165-1173, 1993.