Bone marrow microenvironmental changes in aged mice compromise V(D)J recombinase activity and B cell generation

Seminars in Immunology

Volumn 17, Issue 5, 2005, Pages 347-355

  Labrie III, Joseph E ^a   Borghesi, Lisa ^a,b   Gerstein, Rachel M ^a  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

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

Author keywords

Aging; B cell; Bone marrow stromal cells; Immunoglobulin; Osteoporosis; V(D)J recombination

Indexed keywords

CHEMOKINE; RAG2 PROTEIN; RECOMBINASE; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR PAX5; TRANSCRIPTION FACTOR PU 1;

ADIPOCYTE; AGING; B LYMPHOCYTE; BONE MARROW; BONE MARROW CELL; CELL DIFFERENTIATION; CELL LINE; CELL LINEAGE; CELL MATURATION; CORRELATION ANALYSIS; ENZYME ACTIVITY; GENE CONTROL; GENE EXPRESSION; HEMATOPOIETIC STEM CELL; LYMPHOCYTE COUNT; LYMPHOCYTOPOIESIS; MICROENVIRONMENT; NONHUMAN; OSSIFICATION; OSTEOBLAST; OSTEOPOROSIS; PHYSIOLOGY; PROTEIN EXPRESSION; REVIEW; STROMA CELL;

EID: 23044497567     PISSN: 10445323     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.smim.2005.05.012     Document Type: Article

References (114)

1. G.H. Kline, T.A. Hayden, and N.R. Klinman B cell maintenance in aged mice reflects both increased B cell longevity and decreased B cell generation J Immunol 162 1999 3342 3349
2. R.A. Miller The aging immune system: primer and prospectus Science 273 1996 70 74
3. S. Sambhara, A. Kurichh, R. Miranda, O. James, B. Underdown, and M. Klein Severe impairment of primary but not memory responses to influenza viral antigens in aged mice: costimulation in vivo partially reverses impaired primary immune responses Cell Immunol 210 2001 1 4
4. P. Ghia, F. Melchers, and A.G. Rolink Age-dependent changes in B lymphocyte development in man and mouse Exp Gerontol 35 2000 159 165
5. P. Ghia, E. ten Boekel, A.G. Rolink, and F. Melchers B-cell development: a comparison between mouse and man Immunol Today 19 1998 480 485
6. J.E. Callahan, J.W. Kappler, and P. Marrack Unexpected expansions of CD8-bearing cells in old mice J Immunol 151 1993 6657 6669
7. B. Zheng, S. Han, Y. Takahashi, and G. Kelsoe Immunosenescence and germinal center reaction Immunol Rev 160 1997 63 77
8. S.C. Riley, B.G. Froscher, P.J. Linton, D. Zharhary, K. Marcu, and N.R. Klinman Altered VH gene segment utilization in the response to phosphorylcholine by aged mice J Immunol 143 1989 3798 3805
9. J. LeMaoult, P. Szabo, and M.E. Weksler Effect of age on humoral immunity, selection of the B-cell repertoire and B-cell development Immunol Rev 160 1997 115 126
10. P. Szabo, S. Shen, W. Telford, and M.E. Weksler Impaired rearrangement of IgH V to DJ segments in bone marrow pro-B cells from old mice Cell Immunol 222 2003 78 87
11. F. Li, F. Jin, A. Freitas, P. Szabo, and M.E. Weksler Impaired regeneration of the peripheral B cell repertoire from bone marrow following lymphopenia in old mice Eur J Immunol 31 2001 500 505
12. R.R. Hardy B-cell commitment: deciding on the players Curr Opin Immunol 15 2003 158 165
13. D. Allman, and J.P. Miller Common lymphoid progenitors, early B-lineage precursors, and IL-7: characterizing the trophic and instructive signals underlying early B cell development Immunol Res 27 2003 131 140
14. Y. Baba, R. Pelayo, and P.W. Kincade Relationships between hematopoietic stem cells and lymphocyte progenitors Trends Immunol 25 2004 645 649
15. D. Izon, K. Rudd, W. DeMuth, W.S. Pear, C. Clendenin, and R.C. Lindsley A common pathway for dendritic cell and early B cell development J Immunol 167 2001 1387 1392
16. J.P. Miller, D. Izon, W. DeMuth, R. Gerstein, A. Bhandoola, and D. Allman The earliest step in B lineage differentiation from common lymphoid progenitors is critically dependent upon interleukin 7 J Exp Med 196 2002 705 711
17. D. Allman, A. Sambandam, S. Kim, J.P. Miller, A. Pagan, and D. Well Thymopoiesis independent of common lymphoid progenitors Nat Immunol 4 2003 168 174
18. P.C. Swanson The bounty of RAGs: recombination signal complexes and reaction outcomes Immunol Rev 200 2004 90 114
19. D.G. Schatz V(D)J recombination Immunol Rev 200 2004 5 11
20. M.A. Oettinger, D.G. Schatz, C. Gorka, and D. Baltimore RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination Science 248 1990 1517 1523
21. D.G. Schatz, M.A. Oettinger, and D. Baltimore The V(D)J recombination activating gene, RAG-1 Cell 59 1989 1035 1048
22. U. Grawunder, T.M. Leu, D.G. Schatz, A. Werner, A.G. Rolink, and F. Melchers Down-regulation of RAG1 and RAG2 gene expression in preB cells after functional immunoglobulin heavy chain rearrangement Immunity 3 1995 601 608
23. W. Yu, Z. Misulovin, H. Suh, R.R. Hardy, M. Jankovic, and N. Yannoutsos Coordinate regulation of RAG1 and RAG2 by cell type-specific DNA elements 5′ of RAG2 Science 285 1999 1080 1084
24. M.S. Schlissel Regulating antigen-receptor gene assembly Nat Rev Immunol 3 2003 890 899
25. J. Lauring, and M.S. Schlissel Distinct factors regulate the murine RAG-2 promoter in B- and T-cell lines Mol Cell Biol 19 1999 2601 2612
26. Z.X. Jin, H. Kishi, X.C. Wei, T. Matsuda, S. Saito, and A. Muraguchi Lymphoid enhancer-binding factor-1 binds and activates the recombination- activating gene-2 promoter together with c-Myb and Pax-5 in immature B cells J Immunol 169 2002 3783 3792
27. G.A. Miranda, M. Villalvazo, Z. Galic, J. Alva, R. Abrines, and Y. Yates Combinatorial regulation of the murine RAG-2 promoter by Sp1 and distinct lymphocyte-specific transcription factors Mol Immunol 38 2002 1151 1159
28. T. Kitagawa, K. Mori, H. Kishi, H. Tagoh, T. Nagata, and H. Kurioka Chromatin structure and transcriptional regulation of human RAG-1 gene Blood 88 1996 3785 3791
29. H. Kishi, X.C. Wei, Z.X. Jin, Y. Fujishiro, T. Nagata, and T. Matsuda Lineage-specific regulation of the murine RAG-2 promoter: GATA-3 in T cells and Pax-5 in B cells Blood 95 2000 3845 3852
30. H. Kishi, Z.X. Jin, X.C. Wei, T. Nagata, T. Matsuda, and S. Saito Cooperative binding of c-Myb and Pax-5 activates the RAG-2 promoter in immature B cells Blood 99 2002 576 583
31. Q.F. Wang, J. Lauring, and M.S. Schlissel c-Myb binds to a sequence in the proximal region of the RAG-2 promoter and is essential for promoter activity in T-lineage cells Mol Cell Biol 20 2000 9203 9211
32. I.C. Fong, A.A. Zarrin, G.E. Wu, and N.L. Berinstein Functional analysis of the human RAG 2 promoter Mol Immunol 37 2000 391 402
33. K. Fuller, and U. Storb Identification and characterization of the murine Rag1 promoter Mol Immunol 34 1997 939 954
34. A.A. Zarrin, I. Fong, L. Malkin, P.A. Marsden, and N.L. Berinstein Cloning and characterization of the human recombination activating gene 1 (RAG1) and RAG2 promoter regions J Immunol 159 1997 4382 4394
35. S.T. Brown, G.A. Miranda, Z. Galic, I.Z. Hartman, C.J. Lyon, and R.J. Aguilera Regulation of the RAG-1 promoter by the NF-Y transcription factor J Immunol 158 1997 5071 5074
36. H. Kurioka, H. Kishi, H. Isshiki, H. Tagoh, K. Mori, and T. Kitagawa Isolation and characterization of a TATA-less promoter for the human RAG-1 gene Mol Immunol 33 1996 1059 1066
37. R.J. Monroe, K.J. Seidl, F. Gaertner, S. Han, F. Chen, and J. Sekiguchi RAG2:GFP knockin mice reveal novel aspects of RAG2 expression in primary and peripheral lymphoid tissues Immunity 11 1999 201 212
38. N. Yannoutsos, V. Barreto, Z. Misulovin, A. Gazumyan, W. Yu, and N. Rajewsky A cis element in the recombination activating gene locus regulates gene expression by counteracting a distant silencer Nat Immunol 5 2004 443 450
39. L.Y. Hsu, J. Lauring, H.E. Liang, S. Greenbaum, D. Cado, and Y. Zhuang A conserved transcriptional enhancer regulates RAG gene expression in developing B cells Immunity 19 2003 105 117
40. P. Mombaerts, J. Iacomini, R.S. Johnson, K. Herrup, S. Tonegawa, and V.E. Papaioannou RAG-1-deficient mice have no mature B and T lymphocytes Cell 68 1992 869 877
41. Y. Shinkai, G. Rathbun, K.P. Lam, E.M. Oltz, V. Stewart, and M. Mendelsohn RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement Cell 68 1992 855 867
42. Z. Li, D.I. Dordai, J. Lee, and S. Desiderio A conserved degradation signal regulates RAG-2 accumulation during cell division and links V(D)J recombination to the cell cycle Immunity 5 1996 575 589
43. J. Lee, and S. Desiderio Cyclin A/CDK2 regulates V(D)J recombination by coordinating RAG-2 accumulation and DNA repair Immunity 11 1999 771 781
44. U. Grawunder, D.G. Schatz, T.M. Leu, A. Rolink, and F. Melchers The half-life of RAG-1 protein in precursor B cells is increased in the absence of RAG-2 expression J Exp Med 183 1996 1731 1737
45. R.L. Riley, M.G. Kruger, and J. Elia B cell precursors are decreased in senescent BALB/c mice, but retain normal mitotic activity in vivo and in vitro Clin Immunol Immunopathol 59 1991 301 313
46. J.P. Miller, and D. Allman The decline in B lymphopoiesis in aged mice reflects loss of very early B-lineage precursors J Immunol 171 2003 2326 2330
47. E.M. Sherwood, B.B. Blomberg, W. Xu, C.A. Warner, and R.L. Riley Senescent BALB/c mice exhibit decreased expression of lambda5 surrogate light chains and reduced development within the pre-B cell compartment J Immunol 161 1998 4472 4475
48. R.P. Stephan, V.M. Sanders, and P.L. Witte Stage-specific alterations in murine B lymphopoiesis with age Int Immunol 8 1996 509 518
49. M.E. Weksler, and P. Szabo The effect of age on the B-cell repertoire J Clin Immunol 20 2000 240 249
50. A. Ben-Yehuda, P. Szabo, R. Dyall, and M.E. Weksler Bone marrow declines as a site of B-cell precursor differentiation with age: relationship to thymus involution Proc Natl Acad Sci USA 91 1994 11988 11992
51. E. van der Put, E.M. Sherwood, B.B. Blomberg, and R.L. Riley Aged mice exhibit distinct B cell precursor phenotypes differing in activation, proliferation and apoptosis Exp Gerontol 38 2003 1137 1147
52. M.E. Weksler, M. Goodhardt, and P. Szabo The effect of age on B cell development and humoral immunity Springer Semin Immunopathol 24 2002 35 52
53. R.P. Stephan, D.A. Lill-Elghanian, and P.L. Witte Development of B cells in aged mice: decline in the ability of pro-B cells to respond to IL-7 but not to other growth factors J Immunol 158 1997 1598 1609
54. R.P. Stephan, C.R. Reilly, and P.L. Witte Impaired ability of bone marrow stromal cells to support B-lymphopoiesis with age Blood 91 1998 75 88
55. J.E. Labrie III, A.P. Sah, D.M. Allman, M.P. Cancro, and R.M. Gerstein Bone marrow microenvironmental changes underlie reduced RAG-mediated recombination and B cell generation in aged mice J Exp Med 200 2004 411 423
56. B. Peault In-vitro models of stroma-dependent lymphopoiesis Semin Immunol 7 1995 169 175
57. K. Dorshkind, R. Narayanan, and K.S. Landreth Regulatory cells and cytokines involved in primary B lymphocyte production Adv Exp Med Biol 323 1992 119 123
58. A.M. Baird, R.M. Gerstein, and L.J. Berg The role of cytokine receptor signaling in lymphocyte development Curr Opin Immunol 11 1999 157 166
59. P. Szabo, K. Zhao, I. Kirman, J. Le Maoult, R. Dyall, and W. Cruikshank Maturation of B cell precursors is impaired in thymic-deprived nude and old mice J Immunol 161 1998 2248 2253
60. L. Borghesi, L.-Y. Hsu, J.P. Miller, M. Anderson, L.A. Herzenberg, and M.S. Schlissel B lineage-specific regulation of V(D)J recombinase activity is established in common lymphoid progenitors J Exp Med 199 4 2004 491 502
61. M.T. Anderson, N. Baumgarth, R.P. Haugland, R.M. Gerstein, T. Tjioe, and L.A. Herzenberg Pairs of violet-light-excited fluorochromes for flow cytometric analysis Cytometry 33 1998 435 444
62. M.T. Anderson, I.M. Tjioe, M.C. Lorincz, D.R. Parks, L.A. Herzenberg, and G.P. Nolan Simultaneous fluorescence-activated cell sorter analysis of two distinct transcriptional elements within a single cell using engineered green fluorescent proteins Proc Natl Acad Sci USA 93 1996 8508 8511
63. L. Borghesi, and R.M. Gerstein Developmental separation of V(D)J recombinase expression and initiation of IgH recombination in B lineage progenitors in vivo J Exp Med 199 2004 483 489
64. D.D. Dudley, J. Sekiguchi, C. Zhu, M.J. Sadofsky, S. Whitlow, and J. DeVido Impaired V(D)J recombination and lymphocyte development in core RAG1-expressing mice J Exp Med 198 2003 1439 1450
65. Y. Akamatsu, R. Monroe, D.D. Dudley, S.K. Elkin, F. Gartner, and S.R. Talukder Deletion of the RAG2 C terminus leads to impaired lymphoid development in mice Proc Natl Acad Sci USA 100 2003 1209 1214
66. H.E. Liang, L.Y. Hsu, D. Cado, L.G. Cowell, G. Kelsoe, and M.S. Schlissel The "dispensable" portion of RAG2 is necessary for efficient V-to-DJ rearrangement during B and T cell development Immunity 17 2002 639 651
67. U. von Freeden-Jeffry, P. Vieira, L.A. Lucian, T. McNeil, S.E. Burdach, and R. Murray Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine J Exp Med 181 1995 1519 1526
68. R.G. Goodwin, D. Friend, S.F. Ziegler, R. Jerzy, B.A. Falk, and S. Gimpel Cloning of the human and murine interleukin-7 receptors: demonstration of a soluble form and homology to a new receptor superfamily Cell 60 1990 941 951
69. S. Dias, H. Silva Jr, A. Cumano, and P. Vieira Interleukin-7 is necessary to maintain the B cell potential in common lymphoid progenitors J Exp Med 201 2005 971 979
70. L.A. Borghesi, Y. Yamashita, and P.W. Kincade Heparan sulfate proteoglycans mediate interleukin-7-dependent B lymphopoiesis Blood 93 1999 140 148
71. R. Roberts, J. Gallagher, E. Spooncer, T.D. Allen, F. Bloomfield, and T.M. Dexter Heparan sulphate bound growth factors: a mechanism for stromal cell mediated haemopoiesis Nature 332 1988 376 378
72. M.Y. Gordon, G.P. Riley, S.M. Watt, and M.F. Greaves Compartmentalization of a haematopoietic growth factor (GM-CSF) by glycosaminoglycans in the bone marrow microenvironment Nature 326 1987 403 405
73. M. Schebesta, P.L. Pfeffer, and M. Busslinger Control of pre-BCR signaling by Pax5-dependent activation of the BLNK gene Immunity 17 2002 473 485
74. H. Liang, Q. Chen, A.H. Coles, S.J. Anderson, G. Pihan, and A. Bradley Wnt5a inhibits B cell proliferation and functions as a tumor suppressor in hematopoietic tissue Cancer Cell 4 2003 349 360
75. I. Tsuboi, K. Morimoto, Y. Hirabayashi, G.X. Li, S. Aizawa, and K.J. Mori Senescent B lymphopoiesis is balanced in suppressive homeostasis: decrease in interleukin-7 and transforming growth factor-beta levels in stromal cells of senescence-accelerated mice Exp Biol Med (Maywood) 229 2004 494 502
76. L.W. Updyke, K.S. Cocke, and D. Wierda Age-related changes in production of interleukin-7 (IL-7) by murine long-term bone marrow cultures (LTBMC) Mech Ageing Dev 69 1993 109 117
77. K. Tokoyoda, T. Egawa, T. Sugiyama, B.I. Choi, and T. Nagasawa Cellular niches controlling B lymphocyte behavior within bone marrow during development Immunity 20 2004 707 718
78. E. Seeman Invited review: pathogenesis of osteoporosis J Appl Physiol 95 2003 2142 2151
79. E. Seeman Reduced bone formation and increased bone resorption: rational targets for the treatment of osteoporosis Osteoporos Int 14 Suppl. 3 2003 S2 S8
80. M. Kassem Mesenchymal stem cells: biological characteristics and potential clinical applications Cloning Stem Cells 6 2004 369 374
81. R.G. Edwards Stem cells today: B1. Bone marrow stem cells Reprod Biomed Online 9 2004 541 583
82. J.E. Grove, E. Bruscia, and D.S. Krause Plasticity of bone marrow-derived stem cells Stem Cells 22 2004 487 500
83. S. Ahdjoudj, O. Fromigue, and P.J. Marie Plasticity and regulation of human bone marrow stromal osteoprogenitor cells: potential implication in the treatment of age-related bone loss Histol Histopathol 19 2004 151 157
84. E.J. Moerman, K. Teng, D.A. Lipschitz, and B. Lecka-Czernik Aging activates adipogenic and suppresses osteogenic programs in mesenchymal marrow stroma/stem cells: the role of PPAR-gamma2 transcription factor and TGF-beta/BMP signaling pathways Aging Cell 3 2004 379 389
85. J.A. Kennell, and O.A. Macdougald Wnt signaling inhibits adipogenesis through beta-catenin dependent and independent mechanisms J Biol Chem 2005 [Epub ahead of print]
86. C.N. Bennett, S.E. Ross, K.A. Longo, L. Bajnok, N. Hemati, and K.W. Johnson Regulation of Wnt signaling during adipogenesis J Biol Chem 277 2002 30998 31004
87. S.E. Ross, N. Hemati, K.A. Longo, C.N. Bennett, P.C. Lucas, and R.L. Erickson Inhibition of adipogenesis by Wnt signaling Science 289 2000 950 953
88. T. Reya, M. O'Riordan, R. Okamura, E. Devaney, K. Willert, and R. Nusse Wnt signaling regulates B lymphocyte proliferation through a LEF-1 dependent mechanism Immunity 13 2000 15 24
89. K. Stenderup, J. Justesen, C. Clausen, and M. Kassem Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells Bone 33 2003 919 926
90. A. Kortesidis, A. Zannettino, S. Isenmann, S. Shi, T. Lapidot, and S. Gronthos Stromal derived factor-1 promotes the growth, survival and development of human bone marrow stromal stem cells Blood 105 10 2005 3793 3801
91. T. Egawa, K. Kawabata, H. Kawamoto, K. Amada, R. Okamoto, and N. Fujii The earliest stages of B cell development require a chemokine stromal cell-derived factor/pre-B cell growth-stimulating factor Immunity 15 2001 323 334
92. T. Nagasawa, H. Kikutani, and T. Kishimoto Molecular cloning and structure of a pre-B-cell growth-stimulating factor Proc Natl Acad Sci USA 91 1994 2305 2309
93. Q. Ma, D. Jones, and T.A. Springer The chemokine receptor CXCR4 is required for the retention of B lineage and granulocytic precursors within the bone marrow microenvironment Immunity 10 1999 463 471
94. G. Bain, E.C. Maandag, D.J. Izon, D. Amsen, A.M. Kruisbeek, and B.C. Weintraub E2A proteins are required for proper B cell development and initiation of immunoglobulin gene rearrangements [see comments] Cell 79 1994 885 892
95. R.P. DeKoter, H.J. Lee, and H. Singh PU.1 regulates expression of the interleukin-7 receptor in lymphoid progenitors Immunity 16 2002 297 309
96. H. Lin, and R. Grosschedl Failure of B-cell differentiation in mice lacking the transcription factor EBF Nature 376 1995 263 267
97. A. Nichogiannopoulou, M. Trevisan, S. Neben, C. Friedrich, and K. Georgopoulos Defects in hemopoietic stem cell activity in Ikaros mutant mice J Exp Med 190 1999 1201 1214
98. S.L. Nutt, B. Heavey, A.G. Rolink, and M. Busslinger Commitment to the B-lymphoid lineage depends on the transcription factor Pax5 Nature 401 1999 556 562
99. H. Singh, K.L. Medina, and J.M. Pongubala Contingent gene regulatory networks and B cell fate specification Proc Natl Acad Sci USA 102 2005 4949 4953
100. K.L. Medina, J.M. Pongubala, K.L. Reddy, D.W. Lancki, R. Dekoter, and M. Kieslinger Assembling a gene regulatory network for specification of the B cell fate Dev Cell 7 2004 607 617
101. C.S. Seet, R.L. Brumbaugh, and B.L. Kee Early B cell factor promotes B lymphopoiesis with reduced interleukin 7 responsiveness in the absence of E2A J Exp Med 199 2004 1689 1700
102. G. Bain, E.C. Robanus Maandag, H.P. te Riele, A.J. Feeney, A. Sheehy, and M. Schlissel Both E12 and E47 allow commitment to the B cell lineage Immunity 6 1997 145 154
103. H. Igarashi, S.C. Gregory, T. Yokota, N. Sakaguchi, and P.W. Kincade Transcription from the RAG1 locus marks the earliest lymphocyte progenitors in bone marrow Immunity 17 2002 117 130
104. Y. Zhuang, A. Jackson, L. Pan, K. Shen, and M. Dai Regulation of E2A gene expression in B-lymphocyte development Mol Immunol 40 2004 1165 1177
105. B.L. Kee, and C. Murre Induction of early B cell factor (EBF) and multiple B lineage genes by the basic helix-loop-helix transcription factor E12 J Exp Med 188 1998 699 713
106. T. Ikawa, H. Kawamoto, L.Y. Wright, and C. Murre Long-term cultured E2A-deficient hematopoietic progenitor cells are pluripotent Immunity 20 2004 349 360
107. Y. Zhuang, P. Soriano, and H. Weintraub The helix-loop-helix gene E2A is required for B cell formation Cell 79 1994 875 884
108. Borghesi L, Gerstein RM. E47 is required for recombinase activity in common lymphoid progenitors (submitted for publication).
109. M.W. Quong, A. Martensson, A.W. Langerak, R.R. Rivera, D. Nemazee, and C. Murre Receptor editing and marginal zone B cell development are regulated by the helix-loop-helix protein, E2A J Exp Med 199 2004 1101 1112
110. D. Frasca, D. Nguyen, R.L. Riley, and B.B. Blomberg Decreased E12 and/or E47 transcription factor activity in the bone marrow as well as in the spleen of aged mice J Immunol 170 2003 719 726
111. D. Frasca, E. van der Put, R.L. Riley, and B.B. Blomberg Age-related differences in the E2A-encoded transcription factor E47 in bone marrow-derived B cell precursors and in splenic B cells Exp Gerontol 39 2004 481 489
112. E. van der Put, D. Frasca, A.M. King, B.B. Blomberg, and R.L. Riley Decreased E47 in senescent B cell precursors is stage specific and regulated posttranslationally by protein turnover J Immunol 173 2004 818 827
113. E.M. Sherwood, W. Xu, A.M. King, B.B. Blomberg, and R.L. Riley The reduced expression of surrogate light chains in B cell precursors from senescent BALB/c mice is associated with decreased E2A proteins Mech Ageing Dev 118 2000 45 59
114. R.L. Riley, J. Knowles, and A.M. King Levels of E2A protein expression in B cell precursors are stage-dependent and inhibited by stem cell factor (c-kit ligand) Exp Hematol 30 2002 1412 1418