Developmental regulation of V(D)J recombination and lymphocyte differentiation

Current Opinion in Genetics and Development

Volumn 6, Issue 5, 1996, Pages 603-609

  Willerford, Dennis M ^a,b   Swat, Wojciech ^a   Alt, Frederick W ^a  

^a BOSTON CHILDREN S HOSPITAL   (United States)

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

Author keywords

[No Author keywords available]

Indexed keywords

CIS ACTING ELEMENT; RECOMBINASE;

B LYMPHOCYTE; DEVELOPMENTAL GENETICS; DNA CLEAVAGE; GENE REARRANGEMENT; GENETIC RECOMBINATION; IMMUNOGLOBULIN GENE; LYMPHOCYTE DIFFERENTIATION; PRIORITY JOURNAL; RECEPTOR GENE; REVIEW; T LYMPHOCYTE; T LYMPHOCYTE RECEPTOR GENE; TRANSCRIPTION REGULATION;

EID: 0030272590     PISSN: 0959437X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-437X(96)80090-6     Document Type: Article

References (62)

1. Rothenberg EV. Functionally responsive T cell development. Adv Immunol. 51:1992;185-214.
2. Kisielow P, Von Boehmer H. Development and selection of T cells: facts and puzzles. Adv Immunol. 58:1995;187-209.
3. Chen J, Alt FW. Gene rearrangement and B-cell development. Curr Opin Immunol. 5:1993;194-200.
4. Sleckman BP, Gorman J, Alt FW. Accessibility control of antigen-receptor variable-region gene assembly: role of cis-acting elements. of outstanding interest Annu Rev Immunol. 14:1996;459-481 Detailed review of cis-acting elements and the regulation of V(D)J rearrangement.
5. Godfrey DI, Zlotnick A. Control points in early T-cell development. Immunol Today. 14:1993;547-552.
6. Godfrey DI, Kennedy J, Mombaerts P, Tonegawa S, Zlotnik A. Onset of TCR-β gene rearrangement and role of TCR-β expression during CD3-CD4-CD8-thymocyte differentiation. J Immunol. 152:1994;4783-4792.
7. Schatz DG, Oettinger MA, Schlissel MS. V(D)J recombination: molecular biology and regulation. Annu Rev Immunol. 10:1992;359-383.
8. Alt FW, Oltz EM, Young F, Gorman J, Taccioli G, Chen J. VDJ recombination. Immunol Today. 13:1992;306-314.
9. Mombaerts P, Iacomini J, Johnson RS, Herrup K, Tonegawa S, Papaioannou VE. RAG-1 deficient mice have no mature B and T lymphocytes. Cell. 68:1992;869-877.
10. Shinkai Y, Rathbun G, Lam KP, Oltz EM, Stewart V, Mendelsohn M, Charron J, Datta M, Young F, Stall AM, et al. RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell. 68:1992;855-867.
11. Van Gent DC, McBlane JF, Ramsden DA, Sadofsky MJ, Hesse JE, Gellert M. Initiation of V(D)J recombination in a cell-free system. of outstanding interest Cell. 81:1995;925-934 This paper presents the first description of RSS-specific cleavage in vitro, paving the way for a biochemical understanding of V(D)J recombination. The reaction required supplementation of cell extracts with recombinant Rag-1 and Rag-2 proteins; this observation, as well as the rapid kinetics, implicated the Rag proteins in participating directly in nucleolytic cleavage.
12. McBlane JF, Van Gent DC, Ramsden DA, Romeo C, Cuomo CA, Gellert M, Oettinger MA. Cleavage at a V(D)J recombination signal requires only RAG1 and RAG2 proteins and occurs in two steps. of outstanding interest Cell. 83:1995;387-395 Direct demonstration that purified Rag-1 and Rag-2 proteins cleave DNA at RSS. The reaction proceeds in two stages, producing a blunt end and a covalent hairpin, species which had been detected previously in developing lymphoid tissues.
13. Roth DB, Lindahl T, Gellert M. Repair and recombination. How to make ends meet. Curr Biol. 5:1995;496-499.
14. Eastman QM, Leu TM, Schatz DG. Initiation of V(D)J recombination in vitro obeying the 12/23 rule. of special interest Nature. 380:1996;85-88 See annotation [15].
15. Van Gent DC, Ramsden DA, Gellert M. The Rag-1 and Rag-2 proteins establish the 12/23 rule in V(D)J recombination. of special interest Cell. 85:1996;107-113 Along with [14], this study demonstrates that the physiological specificity of paired RSS cleavage according to the 12/23 rule can be recapitulated in vitro by using recombinant Rag-1 and Rag-2 proteins when the appropriate cation conditions are used. These observations indicate that Rag-1 and Rag-2 play a role in organizing DNA substrates to achieve this coupled reaction.
16. Taccioli GE, Alt FW. Potential targets for autosomal SCID mutations. of outstanding interest Curr Opin Immunol. 7:1995;436-440 A recent review which accounts for each of the genes known to be involved in the V(D)J reaction. The authors present a synthesis of the V(D)J recombination mechanism with the genetics of autosomally inherited severe combined immunodeficiencies, suggesting candidate genes for these disorders.
17. Taccioli GE, Rathbun G, Oltz E, Stamato T, Jeggo PA, Alt FW. Impairment of V(D)J recombination in double-strand break repair mutants. Science. 260:1993;207-210.
18. Blunt T, Finnie NJ, Taccioli GE, Smith GC, Demengeot J, Gottlieb TM, Mizuta R, Varghese AJ, Alt FW, Jeggo PA, et al. Defective DNA-dependent protein kinase activity is linked to V(D)J recombination and DNA repair defects associated with the murine scid mutation. of outstanding interest Cell. 80:1995;813-823 See annotation [19].
19. Kirchgessner CU, Patil CK, Evans JW, Cuomo CA, Fried LM, Carter T, Oettinger MA, Brown JM. DNA-dependent protein kinase (p350) as a candidate a gene for the murine SCID defect. of outstanding interest Science. 267:1995;1178-1183 Along with [18], this study provides evidence that the gene encoding the DNA-dependent protein kinase is responsible for the murine SCID defect, as well at the chinese hamster ovary cell line V-3 mutation.
20. Li Z, Otevrel T, Gao Y, Cheng H-L, Seed B, Stamato TD, Taccioli GE, Alt FW. The XRCC4 gene encodes a novel protein involved in DNA double-strand break repair and V(D)J recombination. of special interest Cell. 83:1995;1079-1089 This study describes the complementation of the radiation sensitive XR-1 chinese hamster ovary mutation (XRCC4) using a cDNA library and isolation of a novel gene which is involved in double-strand break repair and the V(D)J reaction.
21. Bories J-C, Demengeot J, Davidson L, Alt FW. Gene-targeted deletion and replacement mutations of the T-cell receptor beta-chain enhancer: the role of enhancer elements in controlling V(D)J recombination accessibility. of outstanding interest Proc Natl Acad Sci USA. 93:1996;7871-7876 In this report, the authors demonstrate the requirement of the Eβ element for the germline transcription and rearrangement of TCRβ, using the lox/P elements and Cre recombinase to create a subtle mutation in this cis-regulatory element. In addition, the authors show that replacement of the Eβ with the intronic IgH enhancer partially restores TCRβ rearrangement but is not sufficient to target V(D)J recombination to the TCRβ locus in B cells.
22. Chen J, Lansford RL, Stewart V, Young F, Alt FW. Rag-2-deficient blastocyst complementation: an assay of gene function in lymphocyte development. Proc Natl Acad Sci USA. 90:1993;4528-4532.
23. 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. of outstanding interest Proc Natl Acad Sci USA. 93:1996;7877-7881 This study complements [21], using a germline gene targeting approach. The results show that Eβ is absolutely required for TCRβ germline transcription, rearrangement and T-cell development.
24. Gorman J, Van der Stoep N, Monroe R, Cogne M, Davidson L, Alt FW. The lgκ 3' enhancer influences the ratio of lgκ versus lgλ B lymphocytes: altered κ gene rearrangement and expression in 3'κ enhancer-deleted mice. of outstanding interest Immunity. 1996; Mice with a targeted deletion of the 3' κ enhancer have reduced numbers of lgκ+ B cells and increased lgλ+ B cells. This phenotype may reflect a role for this element in both the rearrangement and expression of lgκ.
25. Xu Y, Davidson L, Alt FW, Baltimore D. Deletion of the lgκ light chain intronic enhancer/matrix attachment region impairs but does not abolish VκJκ rearrangement. of outstanding interest Immunity. 4:1996;377-386 See annotation [24]. Mutation of the intronic κ enhancer inhibits rearrangement of the lgκ locus, reducing the generation of lgκ+ B cells.
26. Shinkai Y, Koyasu S, Nakayama K, Murphy KM, Loh DY, Reinhertz El, Alt FW. Restoration of T cell development in RAG-2-deficient mice by functional TCR transgenes. Science. 259:1993;822-825.
27. Spanopoulou E, Roman CA, Corcoran LM, Sclissel MS, Silver DP, Nemazee D, Nussenzweig ML, Shinton SA, Hardy RR, Baltimore D. Functional immunoglobulin transgenes guide ordered B-cell differentiation in Rag-1-deficient mice. Genes Dev. 8:1994;1030-1042.
28. Young F, Ardman B, Shinkai Y, Lansford R, Blackwell TK, Mendelsohn M, Rolink A, Melchers F, Alt FW. Influence of immunoglobulin heavy- and light-chain expression on B-cell differentiation. Genes Dev. 8:1994;1043-1057.
29. Kitamura D, Roes J, Kuhn R, Rajewsky K. A B-cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin μ chain gene. Nature. 350:1991;423-426.
30. Kitamura D, Kudo A, Schaal S, Muller W, Melchers F, Rajewski K. A critical role of lambda 5 protein in B cell development. Cell. 69:1992;823-831.
31. Groettrup M, Ungewiss K, Azogui O, Palacios R, Owen MJ, Hayday AC, Von Boehmer H. A novel disulfide-linked heterodimer on pre-T cells consists of the T cell receptor β chain and a 33 kd glycoprotein. Cell. 75:1993;283-294.
32. Saint-Ruf C, Ungeweiss K, Groettrup M, Bruno L, Fehling HJ, Von Boehmer H. Analysis and expression of a cloned pre-T cell receptor gene. Science. 266:1994;1208-1212.
33. Fehling HJ, Krotkova A, Saint-Ruf C, Von Boehmer H. Crucial role of the pre-T-cell receptor α gene in development of αβ but not γδ T cells. of outstanding interest Nature. 375:1995;795-798 Mice lacking the pre-T-α chain have a severe block in αβ (but not γδ) T cell development at the DN stage despite TCRβ rearrangement, indicating a role for pre-T-α in generating the developmental signal mediating the DN to DP transition.
34. Xu Y, Davidson L, Alt FW, Baltimore D. Function of the pre-T-cell receptor α chain in T-cell development and allelic exclusion at the T-cell receptor β locus. of outstanding interest Proc Natl Acad Sci USA. 93:1996;2169-2173 Similar findings to [33], using Rag-2 blastocyst complementation to analyze the effects of homozygous inactivation of the Pre-T-α chain. Overexpression of a rearranged TCRβ chain does not rescue the double positive thymocyte compartment nor signal allelic exclusion of the endogenous TCRβ locus.
35. Gong S, Nussenzweig MC. Regulation of an early developmental checkpoint in the B cell pathway by lgβ of outstanding interest Science. 272:1996;411-414 A recent study showing that a component of the pre-B cell receptor signaling complex is required in order to efficiently complete the V to DJ rearrangement step for IgH.
36. Frank SJ, Samelson LE, Klausner RD. The structure and signalling functions of the invariant T cell antigen receptor components. Semin Immunol. 2:1990;89-97.
37. Malissen M, Gillet A, Ardouin L. Altered T cell development in mice with a targeted mutation of the CD3-ε gene. EMBO J. 14:1995;4641-4653.
38. Love PE, Shores EW, Johnson MD, Tremblay ML, Lee EJ, Grinberg A, Huang SP, Hayday A, et al. T cell development in mice that lack the ζ chain of the T cell antigen receptor complex. Science. 261:1993;918-921.
39. Liu CP, Ueda R, She J. Abnormal T cell development in CD3-ζ-/- mutant mice and identification of a novel T cell population in the intestine. EMBO J. 12:1993;4863-4875.
40. Malissen M, Gillet A, Rocha B, Trucy J, Vivier E, Boyer C, Kontgen F, Brun N, Mazza G, Spanapoulou E, et al. T cell development in mice lacking the CD3 η/ν gene. EMBO J. 12:1993;4347-4355.
41. Turner M, Mee PJ, Costello P, Williams O, Price AA, Duddy LP, Furlong MT, Geahlen RL, Tybulewicz VLJ. Perinatal lethality and blocked B-cell development in mice lacking the tyrosine kinase Syk. of outstanding interest Nature. 378:1995;298-302 See annotation [42].
42. Cheng AM, Rowley B, Pao W, Hayday A, Bolen JB, Pawson T. Syk tyrosine kinase required for mouse viability and B-cell development. of outstanding interest Nature. 378:1995;303-306 Along with [41], this paper describes B cell development in the absence of Syk tyrosine kinase. There is a severe block at the pro-B cell stage, despite rearrangement if 1gH. The indication is that the developmental signal normally generated at this stage by IGM is delivered via activation of Syk.
43. Nishizumi H, Taniuchi I, Yamanishi Y, Kitamura D, Ilic D, Mori S, Watanabe T, Yamamoto T. Impaired proliferation of peripheral B cells and indication of autoimmune disease in lyn-deficient mice. Immunity. 3:1995;549-560.
44. Hibbs ML, Tarlinton DM, Armes J, Grail D, Hodgson G, Maglitto R, Stacker SA, Dunn AR. Multiple defects in the immune sustem of Lyn-deficient mice, culminating in autoimmune disease. Cell. 83:1995;301-311.
45. Stein PL, Lee HM, Rich S, Soriano P. p59fyn mutant mice display differential signaling in thymocytes and peripheral T cells. Cell. 70:1992;741-750.
46. Khan WN, Alt FW, Gerstein RM, Malynn BA, Larsson I, Rathbun G, Davidson L, Muller S, Kantor AB, Herzenberg LA, et al. Defective B cell development and function in Btk-deficient mice. Immunity. 3:1995;283-299.
47. Kerner JD, Appleby MW, Mohr RN. Impaired expansion of mouse B cell progenitors lacking Btk. Immunity. 3:1995;301-312.
48. Molina TJ, Kishihara K, Siderovski DP. Profound block in thymocyte development in mice lacking p56lck. Nature. 357:1992;161-164.
49. Mombaerts P, Anderson SJ, Perlmutter RM, Mak TW, Tonegawa S. An activated lck transgene promotes thymocyte development in RAG-1 mutant mice. Immunity. 1:1994;261-267.
50. Swat W, Shinkai Y, Davidson L, Alt FW. Activated ras signals differentiation and expansion of CD4+8+ thymocytes. of outstanding interest Proc Natl Acad Sci USA. 93:1996;4683-4687 T-cell development in the Rag-1 mutant background can be reconstituted to the DN thymocyte stage by an activated ras allele, including restoration of normal cell numbers and cellular phenotype. This result suggests that ras activation may be part of the normal signaling sequence for this developmental transition.
51. Mombaerts P, Clarke AR, Rudnicki MA, Iacommi J, Itohara S, Lafaille JJ, Wang L, Ichikawa Y, Jaenisch R, Hooper ML, et al. Mutations in T-cell antigen receptor genes α and β block thymocyte development at different stages. Nature. 360:1992;225-231.
52. Negishi I, Motoyama N, Nakayama K, Nakayama S, Zhang W, Chan AC, Loh D. Essential role for ZAP-70 in both positive and negative selection of thymocytes. of outstanding interest Nature. 376:1995;435-438 Mice lacking Zap-70 are defective in the negative selection of DP thymocytes as well as the DP to SP transition (positive selection). This result underscores how the composition of the antigen receptor signaling complex changes during development.
53. Leonard WJ, Noguchi M, Russell SM, McBride OW. The molecular basis of X-linked severe combined immunodeficiency: the role of the interleukin-2 receptor γ chain as a common γ chain γc. Immunol Rev. 138:1994;61-86.
54. Di Santo JP, Muller W, Guy-Grand D, Fischer A, Rajewsky K. Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor γ chain. of outstanding interest Proc Natl Acad Sci USA. 92:1995;377-381 See annotation [55].
55. Cao X, Shores EW, Hu-Li J, Anver MR, Kelsals BL, Russell SM, Drago J, Noguchi M, Grinberg A, Bloom ET, et al. Defective lymphoid development in mice lacking expression of the common cytokine receptor γ chain. of outstanding interest Immunity. 2:1995;223-238 Along with [54], mice lacking the common lymphokine receptor γ chain have a severe defect in the production of T and B cells, despite a phenotypically normal developmental sequence. This reference also provides a detailed characterization of functional defects of peripheral lymphocytes.
56. Peschon JJ, Morrisey PJ, Grabstein K, Ramsdell FJ, Maraskovsky E, Gliniak BC, Park LS, Ziegler SF, Williams DE, Ware CB, et al. Early lymphocyte expansion is severely impaired in interleukin-7 receptor-deficient mice. J Exp Med. 180:1994;1955.
57. Von Freeden-Jeffrey U, Vieira P, Lucian LA, McNeil T, Burdach SE, Murray R. Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine. J Exp Med. 181:1995;1519-1526.
58. Muegge K, Vila MP, Durum SK. Interleukin-7: a cofactor for V(D)J rearrangement of the T cell receptor β gene. Science. 261:1993;93-95.
59. Thormis DC, Gurniak CB, Tivoli E, Sharpe AH, Berg LJ. Defects in B lymphocyte maturation and T lymphocyte activation in mice lacking Jak3. of outstanding interest Science. 270:1995;794-797 See annotation [60].
60. Nosaka T, Deursen JM, Tripp RA, Thierfelder WE, Witthuhn BA, McMickle AP, Doherty PL, Grosveld GC, Ihle JN, et al. Defective lymphoid development in mice lacking Jak-3. of outstanding interest Science. 270:1995;800-802 Along with [59], this study characterizes the defect in mice lacking Jak-3, which is associated with the common lymphokine receptor γ chain. The phenotypes of these mice resemble the γ chain deficient mice described in [54,55].
61. Russell SM, Tayebi N, Nakajima H. Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development. of outstanding interest Science. 270:1995;797-800 See annotation [62].
62. Macchi P, Villa A, Gillani S, Sacco MG, Frattini A, Porta F, Ugazio AG, Johnston JA, O'Shea JJ, Vezzoni P, et al. Mutations of the Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID). of outstanding interest Nature. 377:1995;65-68 Along with [61], these papers describe patients with a typical phenotype for X-linked SCID with B cells but with an autosomal pattern of inheritance. In each case, a mutation in the Jak-3 gene is described.