Bone marrow microenvironmental changes underlie reduced RAG-mediated recombination and B cell generation in aged mice

Journal of Experimental Medicine

Volumn 200, Issue 4, 2004, Pages 411-423

  Labrie III, Joseph E ^a   Sah, Alex P ^b   Allman, David M ^b   Cancro, Michael P ^b   Gerstein, Rachel M ^a  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Aging; Antibody formation; B lymphocytes; Gene rearrangement; Hematopoietic system

Indexed keywords

GREEN FLUORESCENT PROTEIN; RAG2 PROTEIN; RECOMBINASE;

ADOLESCENT; AGED; AGING; ANIMAL CELL; ANTIBODY PRODUCTION; ARTICLE; B LYMPHOCYTE; BONE MARROW; CONTROLLED STUDY; GENE; GENE EXPRESSION REGULATION; GENE REARRANGEMENT; MICROENVIRONMENT; MOUSE; NONHUMAN; PRE B LYMPHOCYTE; PRIORITY JOURNAL; RAG2 GENE; SIGNAL TRANSDUCTION;

AGING; ANIMALS; B-LYMPHOCYTES; BONE MARROW; BROMODEOXYURIDINE; DNA-BINDING PROTEINS; FLOW CYTOMETRY; GENE EXPRESSION REGULATION; IMMUNITY, CELLULAR; MICE; MICE, INBRED STRAINS; TIME FACTORS; VDJ RECOMBINASES;

EID: 4344599559     PISSN: 00221007     EISSN: None     Source Type: Journal    
DOI: 10.1084/jem.20040845     Document Type: Article

References (50)

1. Sanchez, M., K. Lindroth, E. Sverremark, A. Gonzalez Fernandez, and C. Fernandez. 2001. The response in old mice: positive and negative immune memory after priming in early age. Int. Immunol. 13:1213-1221.
2. Lu, Y.F., and J. Cerny. 2002. Repertoire of antibody response in bone marrow and the memory response are differentially affected in aging mice. J. Immunol. 169:4920-4927.
3. Miller, R.A. 1996. The aging immune system: primer and prospectus. Science. 273:70-74.
4. Looney, R.J., M.S. Hasan, D. Coffin, D. Campbell, A.R. Falsey, J. Kolassa, J.M. Agosti, G.N. Abraham, and T.G. Evans. 2001. Hepatitis B immunization of healthy elderly adults: relationship between naive CD4+ T cells and primary immune response and evaluation of GM-CSF as an adjuvant. J. Clin. Immunol. 21:30-36.
5. Lucas, A.H., and D.C. Reason. 1998. Aging and the immune response to the Haemophilus influenzae type b capsular polysaccharide: retention of the dominant idiotype and antibody function in the elderly. Infect. Immun. 66:1752-1754.
6. Ben-Yehuda, A., P. Szabo, R. Dyall, and M.E. Weksler. 1994. Bone marrow declines as a site of B-cell precursor differentiation with age: relationship to thymus involution. Proc. Natl. Acad. Sci. USA. 91:11988-11992.
7. Ben-Yehuda, A., P. Szabo, and M.E. Weksler. 1994. Age-associated changes in the B-cell repertoire: effect of age on RAG-1 gene expression in murine bone marrow. Immunol. Lett. 40:287-289.
8. Hu, A., D. Ehleiter, A. Ben-Yehuda, R. Schwab, C. Russo, P. Szabo, and M.E. Weksler. 1993. Effect of age on the expressed B cell repertoire: role of B cell subsets. Int. Immunol. 5:1035-1039.
9. LeMaoult, J., P. Szabo, and M.E. Weksler. 1997. Effect of age on humoral immunity, selection of the B-cell repertoire and B-cell development. Immunol. Rev. 160:115-126.
10. van Dijk-Hard, I., I. Soderstrom, S. Feld, D. Holmberg, and I. Lundkvist. 1997. Age-related impaired affinity maturation and differential D-JH gene usage in human VH6-expressing B lymphocytes from healthy individuals. Eur. J. Immunol. 27: 1381-1386.
11. Szabo, P., K. Zhao, I. Kirman, J. LeMaoult, R. Dyall, W. Cruikshank, and M.E. Weksler. 1998. Maturation of B cell precursors is impaired in thymic-deprived nude and old mice. J. Immunol. 161:2248-2253.
12. Szabo, P., S. Shen, and M.E. Weksler. 1999. Age-associated defects in B lymphocyte development. Exp. Gerontol. 34: 431-434.
13. Klinman, N.R., and G.H. Kline. 1997. The B-cell biology of aging. Immunol. Rev. 160:103-114.
14. Kline, G.H., T.A. Hayden, and N.R. Klinman. 1999. B cell maintenance in aged mice reflects both increased B cell longevity and decreased B cell generation. J. Immunol. 162: 3342-3349.
15. Oettinger, M.A., D.G. Schatz, C. Gorka, and D. Baltimore. 1990. RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination. Science. 248:1517-1523.
16. Schatz, D.G., M.A. Oettinger, and D. Baltimore. 1989. The V(D)J recombination activating gene, RAG-1. Cell. 59: 1035-1048.
17. Riley, R.L., M.G. Kruger, and J. Elia. 1991. B cell precursors are decreased in senescent BALB/c mice, but retain normal mitotic activity in vivo and in vitro. Clin. Immunol. Immunopathol. 59:301-313.
18. Stephan, R.P., V.M. Sanders, and P.L. Witte. 1996. Stage-specific alterations in murine B lymphopoiesis with age. Int. Immunol. 8:509-518.
19. Van der Put, E., E.M. Sherwood, B.B. Blomberg, and R.L. Riley. 2003. Aged mice exhibit distinct B cell precursor phenotypes differing in activation, proliferation and apoptosis. Exp. Gerontol. 38:1137-1147.
20. Stephan, R.P., D.A. Lill-Elghanian, and P.L. Witte. 1997. 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. 158:1598-1609.
21. Sherwood, E.M., W. Xu, A.M. King, B.B. Blomberg, and R.L. Riley. 2000. 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. 118:45-59.
22. Stephan, R.P., C.R. Reilly, and P.L. Witte. 1998. Impaired ability of bone marrow stromal cells to support B-lymphopoiesis with age. Blood. 91:75-88.
23. Yu, W., Z. Misulovin, H. Suh, R.R. Hardy, M. Jankovic, N. Yannoutsos, and M.C. Nussenzweig. 1999. Coordinate regulation of RAG1 and RAG2 by cell type-specific DNA elements 5′ of RAG2. Science. 285:1080-1084.
24. Monroe, R.J., K.J. Seidl, F. Gaertner, S. Han, F. Chen, J. Sekiguchi, J. Wang, R. Ferrini, L. Davidson, G. Kelsoe, and F.W. Alt. 1999. RAG2:GFP knockin mice reveal novel aspects of RAG2 expression in primary and peripheral lymphoid tissues. Immunity. 11:201-212.
25. Borghesi, L., L.Y. Hsu, J.P. Miller, M. Anderson, L. Herzenberg, M.S. Schlissel, D. Allman, and R.M. Gerstein. 2004. B lineage-specific regulation of V(D)J recombinase activity is established in common lymphoid progenitors. J. Exp. Med. 199:491-502.
26. Allman, D.M., S.E. Ferguson, V.M. Lentz, and M.P. Cancro. 1993. 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. 151:4431-4444.
27. Lentz, V.M., M.P. Cancro, F.E. Nashold, and C.E. Hayes. 1996. Bcmd governs recruitment of new B cells into the stable peripheral B cell pool in the A/WySnJ mouse. J. Immunol. 157:598-606.
28. Allman, D.M., S.E. Ferguson, and M.P. Cancro. 1992. Peripheral B cell maturation. I. Immature peripheral B cells in adults are heat-stable antigenhi and exhibit unique signaling characteristics. J. Immunol. 149:2533-2540.
29. Sprent, J., and D.F. Tough. 1994. Lymphocyte life-span and memory. Science. 265:1395-1400.
30. Hardy, R.R., C.E. Carmack, S.A. Shinton, J.D. Kemp, and K. Hayakawa. 1991. Resolution and characterization of pro-B and pre-pro-B cell stages in normal mouse bone marrow. J. Exp. Med. 173:1213-1225.
31. Anderson, M.T., N. Baumgarth, R.P. Haugland, R.M. Gerstein, T. Tjioe, and L.A. Herzenberg. 1998. Pairs of violet-light-excited fluorochromes for flow cytometric analysis. Cytometry. 33:435-444.
32. Anderson, M.T., I.M. Tjioe, M.C. Lorincz, D.R. Parks, L.A. Herzenberg, and G.P. Nolan. 1996. 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. 93:8508-8511.
33. Borghesi, L., and R.M. Gerstein. 2004. Developmental separation of V(D)J recombinase expression and initiation of IgH recombination in B lineage progenitors in vivo. J. Exp. Med. 199:483-489.
34. Miller, J.P., and D. Allman. 2003. The decline in B lymphopoiesis in aged mice reflects loss of very early B-lineage precursors. J. Immunol. 171:2326-2330.
35. Tokoyoda, K., T. Egawa, T. Sugiyama, B.I. Choi, and T. Nagasawa. 2004. Cellular niches controlling B lymphocyte behavior within bone marrow during development. Immunity. 20:707-718.
36. Hsu, L.Y., J. Lauring, H.E. Liang, S. Greenbaum, D. Cado, Y. Zhuang, and M.S. Schlissel. 2003. A conserved transcriptional enhancer regulates RAG gene expression in developing B cells. Immunity. 19:105-117.
37. Sigvardsson, M., M. O'Riordan, and R. Grosschedl. 1997. EBF and E47 collaborate to induce expression of the endogenous immunoglobulin surrogate light chain genes. Immunity. 7:25-36.
38. Sherwood, E.M., B.B. Blomberg, W. Xu, C.A. Warner, and R.L. Riley. 1998. Senescent BALB/c mice exhibit decreased expression of lambda5 surrogate light chains and reduced development within the pre-B cell compartment. J. Immunol. 161:4472-4475.
39. Frasca, D., E. Van Der Put, R.L. Riley, and B.B. Blomberg. 2004. Age-related differences in the E2A-encoded transcription factor E47 in bone marrow-derived B cell precursors and in splenic B cells. Exp. Gerontol. 39:481-489.
40. Szabo, P., S. Shen, W. Telford, and M.E. Weksler. 2003. Impaired rearrangement of IgH V to DJ segments in bone marrow pro-B cells from old mice. Cell. Immunol. 222:78-87.
41. Ghia, P., E. ten Boekel, A.G. Rolink, and F. Melchers. 1998. B-cell development: a comparison between mouse and man. Immunol. Today. 19:480-485.
42. Ghia, P., F. Melchers, and A.G. Rolink. 2000. Age-dependent changes in B lymphocyte development in man and mouse. Exp. Gerontol. 35:159-165.
43. Sambhara, S., A. Kurichh, R. Miranda, O. James, B. Underdown, M. Klein, J. Tartaglia, and D. Burt. 2001. 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. 210:1-4.
44. Callahan, J.E., J.W. Kappler, and P. Marrack. 1993. Unexpected expansions of CD8-bearing cells in old mice. J. Immunol. 151:6657-6669.
45. Zheng, B., S. Han, Y. Takahashi, and G. Kelsoe. 1997. Immunosenescence and germinal center reaction. Immunol. Rev. 160:63-77.
46. Riley, S.C., B.G. Froscher, P.J. Linton, D. Zharhary, K. Marcu, and N.R. Klinman. 1989. Altered VH gene segment utilization in the response to phosphorylcholine by aged mice. J. Immunol. 143:3798-3805.
47. Dudley, D.D., J. Sekiguchi, C. Zhu, M.J. Sadofsky, S. Whitlow, J. DeVido, R.J. Monroe, C.H. Bassing, and F.W. Alt. 2003. Impaired V(D)J recombination and lymphocyte development in core RAG1-expressing mice. J. Exp. Med. 198: 1439-1450.
48. Akamatsu, Y., R. Monroe, D.D. Dudley, S.K. Elkin, F. Gartner, S.R. Talukder, Y. Takahama, F.W. Alt, C.H. Bassing, and M.A. Oettinger. 2003. Deletion of the RAG2 C terminus leads to impaired lymphoid development in mice. Proc. Natl. Acad. Sci. USA. 100:1209-1214.
49. Liang, H.E., L.Y. Hsu, D. Cado, L.G. Cowell, G. Kelsoe, and M.S. Schlissel. 2002. The "dispensable" portion of RAG2 is necessary for efficient V-to-DJ rearrangement during B and T cell development. Immunity. 17:639-651.
50. Opstelten, D., and D.G. Osmond. 1983. Pre-B cells in mouse bone marrow: immunofluorescence stathmokinetic studies of the proliferation of cytoplasmic mu-chain-bearing cells in normal mice. J. Immunol. 131:2635-2640.