Conditional disruption of raptor reveals an essential role for mTORC1 in B cell development, survival, and metabolism

Journal of Immunology

Volumn 197, Issue 6, 2016, Pages 2250-2260

  Iwata, Terri N ^a   Ramírez, Julita A ^a   Tsang, Mark ^a   Park, Heon ^a   Margineantu, Daciana H ^b   Hockenbery, David M ^b   Iritani, Brian M ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

^b USA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BREAKPOINT CLUSTER REGION PROTEIN; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; NUCLEAR PROTEIN; PROTEIN BCL XL; RAPAMYCIN; RAPTOR PROTEIN; UNCLASSIFIED DRUG; BCL2L1 PROTEIN, MOUSE; MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1; MTOR PROTEIN, MOUSE; MULTIPROTEIN COMPLEX; PROTEIN BCL X; RPTOR PROTEIN, MOUSE; SIGNAL TRANSDUCING ADAPTOR PROTEIN; TARGET OF RAPAMYCIN KINASE; TRANSCRIPTION FACTOR;

ANIMAL CELL; ANTIBODY PRODUCTION; ARTICLE; B LYMPHOCYTE; BONE MARROW; CELL DEATH; CELL LINEAGE; CELL MATURATION; CELL METABOLISM; CELL PROLIFERATION; CELL SURVIVAL; CELL VIABILITY; CONTROLLED STUDY; FLOW CYTOMETRY; GENE REARRANGEMENT; GLYCOLYSIS; IMMUNOBLOTTING; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN TARGETING; QUANTITATIVE ANALYSIS; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; SPLEEN CELL; ANIMAL; DEFICIENCY; DRUG EFFECTS; GENETICS; IMMUNOLOGY; METABOLISM; PHOSPHORYLATION; PHYSIOLOGY; PRE B LYMPHOCYTE;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ANIMALS; BCL-X PROTEIN; CELL PROLIFERATION; CELL SURVIVAL; GLYCOLYSIS; MICE; MULTIPROTEIN COMPLEXES; PHOSPHORYLATION; PRECURSOR CELLS, B-LYMPHOID; SIGNAL TRANSDUCTION; SIROLIMUS; TOR SERINE-THREONINE KINASES; TRANSCRIPTION FACTORS;

EID: 84988921305     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1600492     Document Type: Article

References (52)

1. Laplante, M., and D. M. Sabatini. 2012. mTOR signaling in growth control and disease. Cell 149: 274-293.
2. Shimobayashi, M., and M. N. Hall. 2014. Making new contacts: the mTOR network in metabolism and signalling crosstalk. Nat. Rev. Mol. Cell Biol. 15: 155-162.
3. Abraham, R. T., and G. J. Wiederrecht. 1996. Immunopharmacology of rapamycin. Annu. Rev. Immunol. 14: 483-510.
4. Powell, J. D., K. N. Pollizzi, E. B. Heikamp, and M. R. Horton. 2012. Regulation of immune responses by mTOR. Annu. Rev. Immunol. 30: 39-68.
5. Liu, C., N. M. Chapman, P. W. F. Karmaus, H. Zeng, and H. Chi. 2015. mTOR and metabolic regulation of conventional and regulatory T cells. J. Leukoc. Biol. 97: 837-847.
6. Donnelly, R. P., R. M. Loftus, S. E. Keating, K. T. Liou, C. A. Biron, C. M. Gardiner, and D. K. Finlay. 2014. mTORC1-dependent metabolic reprogramming is a prerequisite for NK cell effector function. J. Immunol. 193: 4477-4484.
7. Wei, J., K. Yang, and H. Chi. 2014. Cutting edge: discrete functions of mTOR signaling in invariant NKT cell development and NKT17 fate decision. J. Immunol. 193: 4297-4301.
8. Marçais, A., J. Cherfils-Vicini, C. Viant, S. Degouve, S. Viel, A. Fenis, J. Rabilloud, K. Mayol, A. Tavares, J. Bienvenu, et al. 2014. The metabolic checkpoint kinase mTOR is essential for IL-15 signaling during the development and activation of NK cells. Nat. Immunol. 15: 749-757.
9. Hardy, R. R., and K. Hayakawa. 2001. B cell development pathways. Annu. Rev. Immunol. 19: 595-621.
10. Herzog, S., M. Reth, and H. Jumaa. 2009. Regulation of B-cell proliferation and differentiation by pre-B-cell receptor signalling. Nat. Rev. Immunol. 9: 195-205.
11. Reth, M., and P. Nielsen. 2014. Signaling circuits in early B-cell development. Adv. Immunol. 122: 129-175.
12. Clark, M. R., M. Mandal, K. Ochiai, and H. Singh. 2014. Orchestrating B cell lymphopoiesis through interplay of IL-7 receptor and pre-B cell receptor signalling. Nat. Rev. Immunol. 14: 69-80.
13. Limon, J. J., and D. A. Fruman. 2012. Akt and mTOR in B cell activation and differentiation. Front. Immunol. 3: 228.
14. Suzuki, H., Y. Terauchi, M. Fujiwara, S. Aizawa, Y. Yazaki, T. Kadowaki, and S. Koyasu. 1999. Xid-like immunodeficiency in mice with disruption of the p85alpha subunit of phosphoinositide 3-kinase. Science 283: 390-392.
15. Fruman, D. A., S. B. Snapper, C. M. Yballe, L. Davidson, J. Y. Yu, F. W. Alt, and L. C. Cantley. 1999. Impaired B cell development and proliferation in absence of phosphoinositide 3-kinase p85alpha. Science 283: 393-397.
16. Ramadani, F., D. J. Bolland, F. Garcon, J. L. Emery, B. Vanhaesebroeck, A. E. Corcoran, and K. Okkenhaug. 2010. The PI3K isoforms p110alpha and p110delta are essential for pre-B cell receptor signaling and B cell development. Sci. Signal. 3: ra60.
17. Lee, K., L. Heffington, J. Jellusova, K. T. Nam, A. Raybuck, S. H. Cho, J. W. Thomas, R. C. Rickert, and M. Boothby. 2013. Requirement for Rictor in homeostasis and function of mature B lymphoid cells. Blood 122: 2369-2379.
18. Polak, P., N. Cybulski, J. N. Feige, J. Auwerx, M. A. Rüegg, and M. N. Hall. 2008. Adipose-specific knockout of raptor results in lean mice with enhanced mitochondrial respiration. Cell Metab. 8: 399-410.
19. Hobeika, E., S. Thiemann, B. Storch, H. Jumaa, P. J. Nielsen, R. Pelanda, and M. Reth. 2006. Testing gene function early in the B cell lineage in mb1-cre mice. Proc. Natl. Acad. Sci. USA 103: 13789-13794.
20. Hartley, S. B., J. Crosbie, R. Brink, A. B. Kantor, A. Basten, and C. C. Goodnow. 1991. Elimination from peripheral lymphoid tissues of self-reactive B lymphocytes recognizing membrane-bound antigens. Nature 353: 765-769.
21. Fang, W., D. L. Mueller, C. A. Pennell, J. J. Rivard, Y. S. Li, R. R. Hardy, M. S. Schlissel, and T. W. Behrens. 1996. Frequent aberrant immunoglobulin gene rearrangements in pro-B cells revealed by a bcl-xL transgene. Immunity 4: 291-299.
22. Garcia, S., J. DiSanto, and B. Stockinger. 1999. Following the development of a CD4 T cell response in vivo: from activation to memory formation. Immunity 11: 163-171.
23. Habib, T., H. Park, M. Tsang, I. M. de Alborán, A. Nicks, L. Wilson, P. S. Knoepfler, S. Andrews, D. J. Rawlings, R. N. Eisenman, and B. M. Iritani. 2007. Myc stimulates B lymphocyte differentiation and amplifies calcium signaling. J. Cell Biol. 179: 717-731.
24. Park, H., K. Staehling, M. Tsang, M. W. Appleby, M. E. Brunkow, D. Margineantu, D. M. Hockenbery, T. Habib, H. D. Liggitt, G. Carlson, and B. M. Iritani. 2012. Disruption of Fnip1 reveals a metabolic checkpoint controlling B lymphocyte development. Immunity 36: 769-781.
25. Schlissel, M. S., and D. Baltimore. 1989. Activation of immunoglobulin kappa gene rearrangement correlates with induction of germline kappa gene transcription. Cell 58: 1001-1007.
26. Schlissel, M. S., L. M. Corcoran, and D. Baltimore. 1991. Virus-transformed pre-B cells show ordered activation but not inactivation of immunoglobulin gene rearrangement and transcription. J. Exp. Med. 173: 711-720.
27. 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.
28. Dengler, H. S., G. V. Baracho, S. A. Omori, S. Bruckner, K. C. Arden, D. H. Castrillon, R. A. DePinho, and R. C. Rickert. 2008. Distinct functions for the transcription factor Foxo1 at various stages of B cell differentiation. Nat. Immunol. 9: 1388-1398.
29. Venigalla, R. K., V. A. McGuire, R. Clarke, J. C. Patterson-Kane, A. Najafov, R. Toth, P. C. McCarthy, F. Simeons, L. Stojanovski, and J. S. Arthur. 2013. PDK1 regulates VDJ recombination, cell-cycle exit and survival during B-cell development. EMBO J. 32: 1008-1022.
30. Dul, J. L., Y. Argon, T. Winkler, E. ten Boekel, F. Melchers, and I. L. Martensson. 1996. The murine VpreB1 and VpreB2 genes both encode a protein of the surrogate light chain and are co-expressed during B cell development. Eur. J. Immunol. 26: 906-913.
31. Schieke, S. M., D. Phillips, J. P. McCoy, Jr., A. M. Aponte, R.-F. Shen, R. S. Balaban, and T. Finkel. 2006. The mammalian target of rapamycin (mTOR) pathway regulates mitochondrial oxygen consumption and oxidative capacity. J. Biol. Chem. 281: 27643-27652.
32. Morita, M., S.-P. Gravel, V. Chénard, K. Sikström, L. Zheng, T. Alain, V. Gandin, D. Avizonis,M. Arguello, C. Zakaria, et al. 2013. mTORC1 controls mitochondrial activity and biogenesis through 4E-BP-dependent translational regulation. Cell Metab. 18: 698-711.
33. Zhang, Y., T. Hu, C. Hua, J. Gu, L. Zhang, S. Hao, H. Liang, X. Wang, W. Wang, J. Xu, et al. 2014. Rictor is required for early B cell development in bone marrow. PLoS One 9: e103970.
34. Zhang, S., J. A. Readinger, W. DuBois, M. Janka-Junttila, R. Robinson, M. Pruitt, V. Bliskovsky, J. Z. Wu, K. Sakakibara, J. Patel, et al. 2011. Constitutive reductions in mTOR alter cell size, immune cell development, and antibody production. Blood 117: 1228-1238.
35. Hoshii, T., Y. Tadokoro, K. Naka, T. Ooshio, T. Muraguchi, N. Sugiyama, T. Soga, K. Araki, K. Yamamura, and A. Hirao. 2012. mTORC1 is essential for leukemia propagation but not stem cell self-renewal. J. Clin. Invest. 122: 2114-2129.
36. Zhang, S., M. Pruitt, D. Tran, W. Du Bois, K. Zhang, R. Patel, S. Hoover, R. M. Simpson, J. Simmons, J. Gary, et al. 2013. B cell-specific deficiencies in mTOR limit humoral immune responses. J. Immunol. 191: 1692-1703.
37. Limon, J. J., L. So, S. Jellbauer, H. Chiu, J. Corado, S. M. Sykes, M. Raffatellu, and D. A. Fruman. 2014. mTOR kinase inhibitors promote antibody class switching via mTORC2 inhibition. Proc. Natl. Acad. Sci. USA 111: E5076-E5085.
38. Corfe, S. A., and C. J. Paige. 2012. The many roles of IL-7 in B cell development; mediator of survival, proliferation and differentiation. Semin. Immunol. 24: 198-208.
39. Amin, R. H., and M. S. Schlissel. 2008. Foxo1 directly regulates the transcription of recombination-activating genes during B cell development. Nat. Immunol. 9: 613-622.
40. Baracho, G. V., M. H. Cato, Z. Zhu, O. R. Jaren, E. Hobeika, M. Reth, and R. C. Rickert. 2014. PDK1 regulates B cell differentiation and homeostasis. Proc. Natl. Acad. Sci. USA 111: 9573-9578.
41. Young, F., B. Ardman, Y. Shinkai, R. Lansford, T. K. Blackwell, M. Mendelsohn, A. Rolink, F. Melchers, and F. W. Alt. 1994. Influence of immunoglobulin heavy-and light-chain expression on B-cell differentiation. Genes Dev. 8: 1043-1057.
42. Spanopoulou, E., C. A. Roman, L. M. Corcoran, M. S. Schlissel, D. P. Silver, D. Nemazee, M. C. Nussenzweig, S. A. Shinton, R. R. Hardy, and D. Baltimore. 1994. Functional immunoglobulin transgenes guide ordered B-cell differentiation in Rag-1-deficient mice. Genes Dev. 8: 1030-1042.
43. Strasser, A., A. W. Harris, L. M. Corcoran, and S. Cory. 1994. Bcl-2 expression promotes B-but not T-lymphoid development in scid mice. Nature 368: 457-460.
44. Amanna, I. J., J. P. Dingwall, and C. E. Hayes. 2003. Enforced bcl-xL gene expression restored splenic B lymphocyte development in BAFF-R mutant mice. J. Immunol. 170: 4593-4600.
45. Schenone, S., C. Brullo, F. Musumeci, M. Radi, and M. Botta. 2011. ATPcompetitive inhibitors of mTOR: an update. Curr. Med. Chem. 18: 2995-3014.
46. Wander, S. A., B. T. Hennessy, and J. M. Slingerland. 2011. Next-generation mTOR inhibitors in clinical oncology: how pathway complexity informs therapeutic strategy. J. Clin. Invest. 121: 1231-1241.
47. Janes, M. R., J. J. Limon, L. So, J. Chen, R. J. Lim, M. A. Chavez, C. Vu, M. B. Lilly, S. Mallya, S. T. Ong, et al. 2010. Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor. Nat. Med. 16: 205-213.
48. Yang, K., S. Shrestha, H. Zeng, P. W. F. Karmaus, G. Neale, P. Vogel, D. A. Guertin, R. F. Lamb, and H. Chi. 2013. T cell exit from quiescence and differentiation into Th2 cells depend on Raptor-mTORC1-mediated metabolic reprogramming. Immunity 39: 1043-1056.
49. Kojima, H., A. Kobayashi, D. Sakurai, Y. Kanno, H. Hase, R. Takahashi, Y. Totsuka, G. L. Semenza, M. V. Sitkovsky, and T. Kobata. 2010. Differentiation stage-specific requirement in hypoxia-inducible factor-1alpha-regulated glycolytic pathway during murine B cell development in bone marrow. J. Immunol. 184: 154-163.
50. Iritani, B. M., and R. N. Eisenman. 1999. c-Myc enhances protein synthesis and cell size during B lymphocyte development. Proc. Natl. Acad. Sci. USA 96: 13180-13185.
51. Schuhmacher, M., M. S. Staege, A. Pajic, A. Polack, U. H. Weidle, G. W. Bornkamm, D. Eick, and F. Kohlhuber. 1999. Control of cell growth by c-Myc in the absence of cell division. Curr. Biol. 9: 1255-1258.
52. Le, A., A. N. Lane, M. Hamaker, S. Bose, A. Gouw, J. Barbi, T. Tsukamoto, C. J. Rojas, B. S. Slusher, H. Zhang, et al. 2012. Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B cells. Cell Metab. 15: 110-121.