Epigenetic aspects of lymphocyte antigen receptor gene rearrangement or 'when stochasticity completes randomness'

Immunology

Volumn 139, Issue 2, 2013, Pages 141-150

  Jaeger, Sébastien ^a   Fernandez, Bastien ^b   Ferrier, Pierre ^a  

^a CENTRE D IMMUNOLOGIE DE MARSEILLE LUMINY   (France)

^b AIX MARSEILLE UNIVERSITY   (France)

Author keywords

Allelic exclusion; Chromatin; Epigenetics; Immunoglobulin; T cell receptor; V(D)J recombination

Indexed keywords

IMMUNOGLOBULIN; IMMUNOGLOBULIN H; IMMUNOGLOBULIN L GAMMA; IMMUNOGLOBULIN L KAPPA; LYMPHOCYTE ANTIGEN RECEPTOR; RAG1 PROTEIN; RAG2 PROTEIN; RECOMBINASE; T LYMPHOCYTE RECEPTOR ALPHA CHAIN; T LYMPHOCYTE RECEPTOR BETA CHAIN; T LYMPHOCYTE RECEPTOR DELTA CHAIN; T LYMPHOCYTE RECEPTOR GAMMA CHAIN; UNCLASSIFIED DRUG;

ACCESSIBILITY CONTROL ELEMENT; ADAPTIVE IMMUNITY; ARTICLE; CHROMATIN IMMUNOPRECIPITATION; CHROMATIN STRUCTURE; DNA CLEAVAGE; DNA RECOMBINATION; EPIGENETICS; GENE LOCUS; GENE REARRANGEMENT; GENE STRUCTURE; GENETIC REGULATION; HISTONE MODIFICATION; HUMAN; IMMUNOGENETICS; NONHUMAN; PRIORITY JOURNAL; VDJ RECOMBINATION;

ANIMALS; EPIGENESIS, GENETIC; GENE REARRANGEMENT, T-LYMPHOCYTE; HUMANS; MODELS, GENETIC; MODELS, IMMUNOLOGICAL; RECEPTORS, ANTIGEN, T-CELL; STOCHASTIC PROCESSES; T-LYMPHOCYTES; V(D)J RECOMBINATION;

EID: 84876816603     PISSN: 00192805     EISSN: 13652567     Source Type: Journal    
DOI: 10.1111/imm.12057     Document Type: Article

References (118)

1. Hozumi N, Tonegawa S. Evidence for somatic rearrangement of immunoglobulin genes coding for variable and constant regions. Proc Natl Acad Sci U S A 1976; 73:3628-32.
2. Alt FW, Oltz EM, Young F, Gorman J, Taccioli G, Chen J. VDJ recombination. Immunol Today 1992; 13:306-14.
3. Schatz DG. V(D)J recombination. Immunol Rev 2004; 200:5-11.
4. Schatz DG, Baltimore D. Uncovering the V(D)J recombinase. Cell 2004; 116:S103-6, 102 p following S106.
5. Margueron R, Reinberg D. Chromatin structure and the inheritance of epigenetic information. Nat Rev Genet 2010; 11:285-96.
6. Waddington CH. The epigenotype. Endeavour 1942; 1:18-20.
7. Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet 2012; 13:484-92.
8. Franchini DM, Schmitz KM, Petersen-Mahrt SK. 5-Methylcytosine DNA demethylation: more than losing a methyl group. Annu Rev Genet 2012; 46:419-41.
9. Jenuwein T, Allis CD. Translating the histone code. Science 2001; 293:1074-80.
10. Turner BM. Cellular memory and the histone code. Cell 2002; 111:285-91.
11. Henikoff S, Furuyama T, Ahmad K. Histone variants, nucleosome assembly and epigenetic inheritance. Trends Genet 2004; 20:320-6.
12. Mohn F, Schubeler D. Genetics and epigenetics: stability and plasticity during cellular differentiation. Trends Genet 2009; 25:129-36.
13. Turner BM. The adjustable nucleosome: an epigenetic signaling module. Trends Genet 2012; 28:436-44.
14. Nagano T, Fraser P. No-nonsense functions for long noncoding RNAs. Cell 2011; 145:178-81.
15. Rinn JL, Chang HY. Genome regulation by long noncoding RNAs. Annu Rev Biochem 2012; 81:145-66.
16. Dostie J, Bickmore WA. Chromosome organization in the nucleus - charting new territory across the Hi-Cs. Curr Opin Genet Dev 2012; 22:125-31.
17. Fudenberg G, Mirny LA. Higher-order chromatin structure: bridging physics and biology. Curr Opin Genet Dev 2012; 22:115-24.
18. Brack C, Tonegawa S. Variable and constant parts of the immunoglobulin light chain gene of a mouse myeloma cell are 1250 nontranslated bases apart. Proc Natl Acad Sci U S A 1977; 74:5652-6.
19. Alt F, Rosenberg N, Lewis S, Thomas E, Baltimore D. Organization and reorganization of immunoglobulin genes in A-MULV-transformed cells: rearrangement of heavy but not light chain genes. Cell 1981; 27:381-90.
20. Alt FW, Yancopoulos GD, Blackwell TK et al. Ordered rearrangement of immunoglobulin heavy chain variable region segments. EMBO J 1984; 3:1209-19.
21. Yancopoulos GD, Alt FW. Developmentally controlled and tissue-specific expression of unrearranged VH gene segments. Cell 1985; 40:271-81.
22. Yancopoulos GD, Blackwell TK, Suh H, Hood L, Alt FW. Introduced T cell receptor variable region gene segments recombine in pre-B cells: evidence that B and T cells use a common recombinase. Cell 1986; 44:251-9.
23. Blackwell TK, Moore MW, Yancopoulos GD, Suh H, Lutzker S, Selsing E, Alt FW. Recombination between immunoglobulin variable region gene segments is enhanced by transcription. Nature 1986; 324:585-9.
24. Alt FW, Blackwell TK, DePinho RA, Reth MG, Yancopoulos GD. Regulation of genome rearrangement events during lymphocyte differentiation. Immunol Rev 1986; 895-30.
25. Gellert M. V(D)J recombination: RAG proteins, repair factors, and regulation. Annu Rev Biochem 2002; 71:101-32.
26. Schatz DG, Spanopoulou E. Biochemistry of V(D)J recombination. Curr Top Microbiol Immunol 2005; 290:49-85.
27. Schatz DG, Swanson PC. V(D)J recombination: mechanisms of initiation. Annu Rev Genet 2011; 45:167-202.
28. Jones JM, Gellert M. Ordered assembly of the V(D)J synaptic complex ensures accurate recombination. EMBO J 2002; 21:4162-71.
29. Mundy CL, Patenge N, Matthews AG, Oettinger MA. Assembly of the RAG1/RAG2 synaptic complex. Mol Cell Biol 2002; 22:69-77.
30. Curry JD, Geier JK, Schlissel MS. Single-strand recombination signal sequence nicks in vivo: evidence for a capture model of synapsis. Nat Immunol 2005; 6:1272-9.
31. Ji Y, Resch W, Corbett E, Yamane A, Casellas R, Schatz DG. The in vivo pattern of binding of RAG1 and RAG2 to antigen receptor loci. Cell 2010; 141:419-31.
32. Sleckman BP. Lymphocyte antigen receptor gene assembly: multiple layers of regulation. Immunol Res 2005; 32:253-8.
33. Lieber MR. The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu Rev Biochem 2010; 79:181-211.
34. Boboila C, Alt FW, Schwer B. Classical and alternative end-joining pathways for repair of lymphocyte-specific and general DNA double-strand breaks. Adv Immunol 2012; 116:1-49.
35. Fugmann SD. The origins of the Rag genes - from transposition to V(D)J recombination. Semin Immunol 2010; 22:10-6.
36. Hencken CG, Li X, Craig NL. Functional characterization of an active Rag-like transposase. Nat Struct Mol Biol 2012; 19:834-6.
37. Dadi S, Le Noir S, Asnafi V, Beldjord K, Macintyre EA. Normal and pathological VDJ recombination: contribution of the understanding of human lymphoid malignancies. Adv Exp Med Biol 2009; 650:180-94.
38. Deriano L, Chaumeil J, Coussens M et al. The RAG2 C terminus suppresses genomic instability and lymphomagenesis. Nature 2011; 471:119-23.
39. Burnet FM. The Clonal Selection Theory of Acquired Immunity. Cambridge: The University Press, 1959.
40. Kisielow P, von Boehmer H. Development and selection of T cells: facts and puzzles. Adv Immunol 1995; 58:87-208.
41. Rajewsky K. Clonal selection and learning in the antibody system. Nature 1996; 381:751-8.
42. Mostoslavsky R, Alt FW, Rajewsky K. The lingering enigma of the allelic exclusion mechanism. Cell 2004; 118:539-44.
43. Brady BL, Steinel NC, Bassing CH. Antigen receptor allelic exclusion: an update and reappraisal. J Immunol 2010; 185:3801-8.
44. Bolland DJ, Wood AL, Johnston CM, Bunting SF, Morgan G, Chakalova L, Fraser PJ, Corcoran AE. Antisense intergenic transcription in V(D)J recombination. Nat Immunol 2004; 5:630-7.
45. Bolland DJ, Wood AL, Afshar R, Featherstone K, Oltz EM, Corcoran AE. Antisense intergenic transcription precedes Igh D-to-J recombination and is controlled by the intronic enhancer Emu. Mol Cell Biol 2007; 27:5523-33.
46. Ferrier P, Krippl B, Blackwell TK et al. Separate elements control DJ and VDJ rearrangement in a transgenic recombination substrate. EMBO J 1990; 9:117-25.
47. Capone M, Watrin F, Fernex C, Horvat B, Krippl B, Scollay R, Ferrier P. TCRα and TCRβ gene enhancers confer tissue- and stage-specificity on V(D)J recombination events. EMBO J 1993; 12:4335-46.
48. Lauzurica P, Krangel MS. Temporal and lineage-specific control of T cell receptor α/δ gene rearrangement by T cell receptor α and δ enhancers. J Exp Med 1994; 179:1913-21.
49. Lauzurica P, Krangel MS. Enhancer-dependent and -independent steps in the rearrangement of a human T cell receptor δ transgene. J Exp Med 1994; 179:43-55.
50. Bassing CH, Swat W, Alt FW. The mechanism and regulation of chromosomal V(D)J recombination. Cell 2002; 109(Suppl):S45-55.
51. Bories JC, Demengeot J, Davidson L, Alt FW. Gene-targeted deletion and replacement mutations of the T-cell receptor β-chain enhancer: the role of enhancer elements in controlling V(D)J recombination accessibility. Proc Natl Acad Sci U S A 1996; 93:7871-6.
52. Bouvier G, Watrin F, Naspetti M, Verthuy C, Naquet P, Ferrier P. Deletion of the mouse T-cell receptor β gene enhancer blocks αβ T-cell development. Proc Natl Acad Sci U S A 1996; 93:7877-81.
53. Villey I, Caillol D, Selz F, Ferrier P, de Villartay JP. Defect in rearrangement of the most 5′ TCR-J α following targeted deletion of T early α (TEA): implications for TCR α locus accessibility. Immunity 1996; 5:331-42.
54. Sleckman BP, Bardon CG, Ferrini R, Davidson L, Alt FW. Function of the TCR α enhancer in αβ and γδ T cells. Immunity 1997; 7:505-15.
55. Whitehurst CE, Chattopadhyay S, Chen J. Control of V(D)J recombinational accessibility of the Dβ1 gene segment at the TCR β locus by a germline promoter. Immunity 1999; 10:313-22.
56. Mathieu N, Hempel WM, Spicuglia S, Verthuy C, Ferrier P. Chromatin remodeling by the T cell receptor (TCR)-β gene enhancer during early T cell development: implications for the control of TCR-β locus recombination. J Exp Med 2000; 192:625-36.
57. Whitehurst CE, Schlissel MS, Chen J. Deletion of germline promoter PD β1 from the TCR β locus causes hypermethylation that impairs D β1 recombination by multiple mechanisms. Immunity 2000; 13:703-14.
58. Lazorchak AS, Schlissel MS, Zhuang Y. E2A and IRF-4/Pip promote chromatin modification and transcription of the immunoglobulin κ locus in pre-B cells. Mol Cell Biol 2006; 26:810-21.
59. Agata Y, Tamaki N, Sakamoto S, Ikawa T, Masuda K, Kawamoto H, Murre C. Regulation of T cell receptor β gene rearrangements and allelic exclusion by the helix-loop-helix protein, E47. Immunity 2007; 27:871-84.
60. Johnson K, Hashimshony T, Sawai CM, Pongubala JM, Skok JA, Aifantis I, Singh H. Regulation of immunoglobulin light-chain recombination by the transcription factor IRF-4 and the attenuation of interleukin-7 signaling. Immunity 2008; 28:335-45.
61. D'Cruz LM, Knell J, Fujimoto JK, Goldrath AW. An essential role for the transcription factor HEB in thymocyte survival, Tcra rearrangement and the development of natural killer T cells. Nat Immunol 2010; 11:240-9.
62. Zhou XF, Yu J, Chang M, Zhang M, Zhou D, Cammas F, Sun SC. TRIM28 mediates chromatin modifications at the TCRα enhancer and regulates the development of T and natural killer T cells. Proc Natl Acad Sci U S A 2012; 109:20083-88.
63. Stanhope-Baker P, Hudson KM, Shaffer AL, Constantinescu A, Schlissel MS. Cell type-specific chromatin structure determines the targeting of V(D)J recombinase activity in vitro. Cell 1996; 85:887-97.
64. McMurry MT, Krangel MS. A role for histone acetylation in the developmental regulation of VDJ recombination. Science 2000; 287:495-8.
65. Spicuglia S, Kumar S, Yeh J-H, Vachez E, Chasson L, Gorbatch S, Cautres J, Ferrier P. Promoter activation by enhancer-dependent and -independent loading of activator and coactivator complexes. Mol Cell 2002; 10:1479-87.
66. Morshead KB, Ciccone DN, Taverna SD, Allis CD, Oettinger MA. Antigen receptor loci poised for V(D)J rearrangement are broadly associated with BRG1 and flanked by peaks of histone H3 dimethylated at lysine 4. Proc Natl Acad Sci U S A 2003; 100:11577-82.
67. Espinoza CR, Feeney AJ. The extent of histone acetylation correlates with the differential rearrangement frequency of individual VH genes in pro-B cells. J Immunol 2005; 175:6668-75.
68. Espinoza CR, Feeney AJ. Chromatin accessibility and epigenetic modifications differ between frequently and infrequently rearranging V(H) genes. Mol Immunol 2007; 44:2675-85.
69. Chakraborty T, Perlot T, Subrahmanyam R et al. A 220-nucleotide deletion of the intronic enhancer reveals an epigenetic hierarchy in immunoglobulin heavy chain locus activation. J Exp Med 2009; 206:1019-27.
70. Osipovich O, Milley R, Meade A, Tachibana M, Shinkai Y, Krangel MS, Oltz EM. Targeted inhibition of V(D)J recombination by a histone methyltransferase. Nat Immunol 2004; 5:309-16.
71. Abarrategui I, Krangel MS. Regulation of T cell receptor-α gene recombination by transcription. Nat Immunol 2006; 7:1109-15.
72. Callebaut I, Mornon JP. The V(D)J recombination activating protein RAG2 consists of a six-bladed propeller and a PHD fingerlike domain, as revealed by sequence analysis. Cell Mol Life Sci 1998; 54:880-91.
73. Elkin SK, Ivanov D, Ewalt M et al. A PHD finger motif in the C terminus of RAG2 modulates recombination activity. J Biol Chem 2005; 280:28701-10.
74. Matthews AG, Kuo AJ, Ramon-Maiques S et al. RAG2 PHD finger couples histone H3 lysine 4 trimethylation with V(D)J recombination. Nature 2007; 450:1106-10.
75. Liu Y, Subrahmanyam R, Chakraborty T, Sen R, Desiderio S. A plant homeodomain in RAG-2 that binds hypermethylated lysine 4 of histone H3 is necessary for efficient antigen-receptor-gene rearrangement. Immunity 2007; 27:561-71.
76. Shimazaki N, Tsai AG, Lieber MR. H3K4me3 stimulates the V(D)J RAG complex for both nicking and hairpinning in trans in addition to tethering in cis: implications for translocations. Mol Cell 2009; 34:535-44.
77. Grundy GJ, Yang W, Gellert M. Autoinhibition of DNA cleavage mediated by RAG1 and RAG2 is overcome by an epigenetic signal in V(D)J recombination. Proc Natl Acad Sci U S A 2010; 107:22487-92.
78. Wang G, Dhar K, Swanson PC, Levitus M, Chang Y. Real-time monitoring of RAG-catalyzed DNA cleavage unveils dynamic changes in coding end association with the coding end complex. Nucleic Acids Res 2012; 40:6082-96.
79. Ji Y, Little AJ, Banerjee JK, Hao B, Oltz EM, Krangel MS, Schatz DG. Promoters, enhancers, and transcription target RAG1 binding during V(D)J recombination. J Exp Med 2010; 207:2809-16.
80. Schatz DG, Ji Y. Recombination centres and the orchestration of V(D)J recombination. Nat Rev Immunol 2011; 11:251-63.
81. H junctions. Nat Immunol 2012; 13:1205-12.
82. Kosak ST, Skok JA, Medina KL, Riblet R, Le Beau MM, Fisher AG, Singh H. Subnuclear compartmentalization of immunoglobulin loci during lymphocyte development. Science 2002; 296:158-62.
83. Roldán E, Fuxa M, Chong W, Martinez D, Novatchkova M, Busslinger M, Skok JA. Locus 'decontraction' and centromeric recruitment contribute to allelic exclusion of the immunoglobulin heavy-chain gene. Nat Immunol 2005; 6:31-41.
84. Skok JA, Gisler R, Novatchkova M, Farmer D, de LW, Busslinger M. Reversible contraction by looping of the Tcrα and Tcrβ loci in rearranging thymocytes. Nat Immunol 2007; 8:378-87.
85. Shih HY, Krangel MS. Distinct contracted conformations of the Tcra/Tcrd locus during Tcra and Tcrd recombination. J Exp Med 2010; 207:1835-41.
86. Jhunjhunwala S, van Zelm MC, Peak MM et al. The 3D structure of the immunoglobulin heavy-chain locus: implications for long-range genomic interactions. Cell 2008; 133:265-79.
87. Fuxa M, Skok J, Souabni A, Salvagiotto G, Roldan E, Busslinger M. Pax5 induces V-to-DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene. Genes Dev 2004; 18:411-22.
88. Liu H, Schmidt-Supprian M, Shi Y et al. Yin Yang 1 is a critical regulator of B-cell development. Genes Dev 2007; 21:1179-89.
89. Reynaud D, Demarco A, Reddy L et al. Regulation of B cell fate commitment and immunoglobulin heavy-chain gene rearrangements by Ikaros. Nat Immunol 2008; 9:927-36.
90. Ebert A, McManus S, Tagoh H et al. The distal V(H) gene cluster of the Igh locus contains distinct regulatory elements with Pax5 transcription factor-dependent activity in pro-B cells. Immunity 2011; 34:175-87.
91. Degner SC, Verma-Gaur J, Wong TP et al. CCCTC-binding factor (CTCF) and cohesin influence the genomic architecture of the Igh locus and antisense transcription in pro-B cells. Proc Natl Acad Sci U S A 2011; 108:9566-71.
92. Seitan VC, Hao B, Tachibana-Konwalski K et al. A role for cohesin in T-cell-receptor rearrangement and thymocyte differentiation. Nature 2011; 476:467-71.
93. Guo C, Yoon HS, Franklin A et al. CTCF-binding elements mediate control of V(D)J recombination. Nature 2011; 477:424-30.
94. Ribeiro de Almeida C, Stadhouders R, de Bruijn MJ et al. The DNA-binding protein CTCF limits proximal Vκ recombination and restricts κ enhancer interactions to the immunoglobulin κ light chain locus. Immunity 2011; 35:501-13.
95. Shih HY, Verma-Gaur J, Torkamani A, Feeney AJ, Galjart N, Krangel MS. Tcra gene recombination is supported by a Tcra enhancer- and CTCF-dependent chromatin hub. Proc Natl Acad Sci U S A 2012; 109:E3493-502.
96. Seitan VC, Krangel MS, Merkenschlager M. Cohesin, CTCF and lymphocyte antigen receptor locus rearrangement. Trends Immunol 2012; 33:153-9.
97. Chaumeil J, Skok JA. The role of CTCF in regulating V(D)J recombination. Curr Opin Immunol 2012; 24:153-9.
98. Ribeiro de Almeida C, Stadhouders R, Thongjuea S, Soler E, Hendriks RW. DNA-binding factor CTCF and long-range gene interactions in V(D)J recombination and oncogene activation. Blood 2012; 119:6209-18.
99. Verma-Gaur J, Torkamani A, Schaffer L, Head SR, Schork NJ, Feeney AJ. Noncoding transcription within the Igh distal VH region at PAIR elements affects the 3D structure of the Igh locus in pro-B cells. Proc Natl Acad Sci U S A 2012; 109:17004-9.
100. Jhunjhunwala S, van Zelm MC, Peak MM, Murre C. Chromatin architecture and the generation of antigen receptor diversity. Cell 2009; 138:435-48.
101. Lucas JS, Bossen C, Murre C. Transcription and recombination factories: common features? Curr Opin Cell Biol 2011; 23:318-24.
102. Bates JG, Cado D, Nolla H, Schlissel MS. Chromosomal position of a VH gene segment determines its activation and inactivation as a substrate for V(D)J recombination. J Exp Med 2007; 204:3247-56.
103. Mostoslavsky R, Singh N, Tenzen T et al. Asynchronous replication and allelic exclusion in the immune system. Nature 2001; 414:221-5.
104. Farago M, Rosenbluh C, Tevlin M et al. Clonal allelic predetermination of immunoglobulin-κ rearrangement. Nature 2012; 490:561-5.
105. Goldmit M, Ji Y, Skok J, Roldan E, Jung S, Cedar H, Bergman Y. Epigenetic ontogeny of the Igk locus during B cell development. Nat Immunol 2005; 6:198-203.
106. Cedar H, Bergman Y. Choreography of Ig allelic exclusion. Curr Opin Immunol 2008; 20:308-17.
107. Hewitt SL, Yin B, Ji Y et al. RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning of immunoglobulin loci. Nat Immunol 2009; 10:655-64. Published erratum appeared in 2009 Nat. Immunol. 2010:1034 and 2010 Nat. Immunol. 2011:2355-2356002E
108. Lutz J, Heideman MR, Roth E et al. Pro-B cells sense productive immunoglobulin heavy chain rearrangement irrespective of polypeptide production. Proc Natl Acad Sci U S A 2011; 108:10644-9.
109. Schlimgen RJ, Reddy KL, Singh H, Krangel MS. Initiation of allelic exclusion by stochastic interaction of Tcrβ alleles with repressive nuclear compartments. Nat Immunol 2008; 9:802-9.
110. Liang H-E, Hsu L-Y, Cado D, Schlissel MS. Variegated transcriptional activation of the immunoglobulin κ locus in pre-b cells contributes to the allelic exclusion of light-chain expression. Cell 2004; 118:19-29.
111. Farcot E, Bonnet M, Jaeger S, Spicuglia S, Fernandez B, Ferrier P. TCRβ allelic exclusion in dynamical models of V(D)J recombination based on allele independence. J Immunol 2010; 185:1622-32.
112. Eldar A, Elowitz MB. Functional roles for noise in genetic circuits. Nature 2010; 467:167-73.
113. Balazsi G, van Oudenaarden A, Collins JJ. Cellular decision making and biological noise: from microbes to mammals. Cell 2011; 144:910-25.
114. + T cells reveals new insights in gene recombination. EMBO J 2012; 31:1666-78. Addendum, EMBO J 31, 4247-4248 (2012).
115. Murugan A, Mora T, Walczak AM, Callan CG Jr. Statistical inference of the generation probability of T-cell receptors from sequence repertoires. Proc Natl Acad Sci U S A 2012; 109:16161-6.
116. Ndifon W, Gal H, Shifrut E et al. Chromatin conformation governs T-cell receptor Jβ gene segment usage. Proc Natl Acad Sci U S A 2012; 109:15865-70.
117. Thuderoz F, Simonet MA, Hansen O et al. Numerical modelling of the V-J combinations of the T cell receptor TRA/TRD locus. PLoS Comput Biol 2010; 6:e1000682.
118. Murray JM, Messier T, Rivers J, O'Neil JPl, Walker VE, Vacek PM, Finette BA. V(D)J Recombinase-Mediated TCR β locus gene usage and coding joint processing in peripheral T cells during perinatal and pediatric development. J Immunol 2012; 189:2356-64.