mTOR activation promotes plasma cell differentiation and bypasses XBP-1 for immunoglobulin secretion

Molecular and Cellular Biology

Volumn 35, Issue 1, 2015, Pages 153-166

  Benhamron, Sandrine ^a   Pattanayak, Shakti ^a   Berger, Michael ^b   Tirosh, Boaz ^a  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^b HEBREW UNIVERSITY   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

GLYCOPROTEIN; GLYCOPROTEIN LY6C; IMMUNOGLOBULIN; MAMMALIAN TARGET OF RAPAMYCIN; PROTEIN; TUBER SCLEROSIS COMPLEX 1 PROTEIN; UNCLASSIFIED DRUG; X BOX BINDING PROTEIN 1; CD19 ANTIGEN; DNA BINDING PROTEIN; IMMUNOGLOBULIN A; LY ANTIGEN; LY-6C ANTIGEN, MOUSE; REGULATORY FACTOR X TRANSCRIPTION FACTORS; TARGET OF RAPAMYCIN KINASE; TRANSCRIPTION FACTOR; TUBEROUS SCLEROSIS COMPLEX 1 PROTEIN; TUMOR SUPPRESSOR PROTEIN;

ANIMAL CELL; ARTICLE; B LYMPHOCYTE DIFFERENTIATION; CELL LINEAGE; CELL MATURATION; CONTROLLED STUDY; ENDOPLASMIC RETICULUM; ENZYME ACTIVATION; GENE DELETION; GENE EXPRESSION PROFILING; GENE INACTIVATION; GENE TARGETING; IMMUNOGLOBULIN PRODUCTION; LYMPHOCYTE FUNCTION; LYMPHOCYTE STRUCTURE; MOUSE; NONHUMAN; PLASMA CELL; PROTEIN ANALYSIS; PROTEIN PROTEIN INTERACTION; PROTEIN SYNTHESIS; TRANSCRIPTION REGULATION; UNFOLDED PROTEIN RESPONSE; ANIMAL; B LYMPHOCYTE; BAGG ALBINO MOUSE; BLOOD; BONE MARROW CELL; CELL DIFFERENTIATION; CYTOLOGY; ENZYME LINKED IMMUNOSORBENT ASSAY; KNOCKOUT MOUSE; METABOLISM; PHOSPHORYLATION; TRANSMISSION ELECTRON MICROSCOPY;

MAMMALIA; MUS;

ANIMALS; ANTIGENS, CD19; ANTIGENS, LY; B-LYMPHOCYTES; BONE MARROW CELLS; CELL DIFFERENTIATION; DNA-BINDING PROTEINS; ENZYME-LINKED IMMUNOSORBENT ASSAY; IMMUNOGLOBULIN A; IMMUNOGLOBULINS; MICE; MICE, INBRED BALB C; MICE, KNOCKOUT; MICROSCOPY, ELECTRON, TRANSMISSION; PHOSPHORYLATION; TOR SERINE-THREONINE KINASES; TRANSCRIPTION FACTORS; TUMOR SUPPRESSOR PROTEINS; UNFOLDED PROTEIN RESPONSE;

EID: 84920025530     PISSN: 02707306     EISSN: 10985549     Source Type: Journal    
DOI: 10.1128/MCB.01187-14     Document Type: Article

References (46)

1. Ron D, Walter P. 2007. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 8:519-529. http://dx.doi.org/10.1038/nrm2199.
2. Aragon IV, Barrington RA, Jackowski S, Mori K, Brewer JW. 2012. The specialized unfolded protein response of B lymphocytes: ATF6alphaindependent development of antibody-secreting B cells. Mol Immunol 51:347-355. http://dx.doi.org/10.1016/j.molimm.2012.04.001.
3. Gass JN, Jiang HY, Wek RC, Brewer JW. 2008. The unfolded protein response of B-lymphocytes: PERK-independent development of antibody- secreting cells. Mol Immunol 45:1035-1043. http://dx.doi.org/10.1016/j.molimm.2007.07.029.
4. Iwakoshi NN, Lee AH, Vallabhajosyula P, Otipoby KL, Rajewsky K, Glimcher LH. 2003. Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1. Nat Immunol 4:321-329. http://dx.doi.org/10.1038/ni907.
5. Taubenheim N, Tarlinton DM, Crawford S, Corcoran LM, Hodgkin PD, Nutt SL. 2012. High rate of antibody secretion is not integral to plasma cell differentiation as revealed by XBP-1 deficiency. J Immunol 189:3328-3338. http://dx.doi.org/10.4049/jimmunol.1201042.
6. Tirosh B, Iwakoshi NN, Glimcher LH, Ploegh HL. 2005. XBP-1 specifically promotes IgM synthesis and secretion, but is dispensable for degradation of glycoproteins in primary B cells. J Exp Med 202:505-516. http://dx.doi.org/10.1084/jem.20050575.
7. Benhamron S, Hadar R, Iwawaky T, So JS, Lee AH, Tirosh B. 2014. Regulated IRE1-dependent decay participates in curtailing immunoglobulin secretion from plasma cells. Eur J Immunol 44:867-876. http://dx.doi.org/10.1002/eji.201343953.
8. Sarbassov DD, Ali SM, Sengupta S, Sheen JH, Hsu PP, Bagley AF, Markhard AL, Sabatini DM. 2006. Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell 22:159-168. http://dx.doi.org/10.1016/j.molcel.2006.03.029.
9. Sengupta S, Peterson TR, Sabatini DM. 2010. Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress. Mol Cell 40: 310-322. http://dx.doi.org/10.1016/j.molcel.2010.09.026.
10. Kamada Y, Funakoshi T, Shintani T, Nagano K, Ohsumi M, Ohsumi Y. 2000. Tor-mediated induction of autophagy via an Apg1 protein kinase complex. J Cell Biol 150:1507-1513. http://dx.doi.org/10.1083/jcb.150.6.1507.
11. Menon S, Manning BD. 2008. Common corruption of the mTOR signaling network in human tumors. Oncogene 27(Suppl 2):S43-S51. http://dx.doi.org/10.1038/onc.2009.352.
12. Powell JD, Delgoffe GM. 2010. The mammalian target of rapamycin: linking T cell differentiation, function, and metabolism. Immunity 33: 301-311. http://dx.doi.org/10.1016/j.immuni.2010.09.002.
13. Donahue AC, Fruman DA. 2007. Distinct signaling mechanisms activate the target of rapamycin in response to different B-cell stimuli. Eur J Immunol 37:2923-2936. http://dx.doi.org/10.1002/eji.200737281.
14. Ozcan U, Ozcan L, Yilmaz E, Duvel K, Sahin M, Manning BD, Hotamisligil GS. 2008. Loss of the tuberous sclerosis complex tumor suppressors triggers the unfolded protein response to regulate insulin signaling and apoptosis. Mol Cell 29:541-551. http://dx.doi.org/10.1016/j.molcel.2007.12.023.
15. Weichhart T, Costantino G, Poglitsch M, Rosner M, Zeyda M, Stuhlmeier KM, Kolbe T, Stulnig TM, Horl WH, Hengstschlager M, Muller M, Saemann MD. 2008. The TSC-mTOR signaling pathway regulates the innate inflammatory response. Immunity 29:565-577. http://dx.doi.org/10.1016/j.immuni.2008.08.012.
16. Goldfinger M, Shmuel M, Benhamron S, Tirosh B. 2011. Protein synthesis in plasma cells is regulated by crosstalk between endoplasmic reticulum stress and mTOR signaling. Eur J Immunol 41:491-502. http://dx.doi.org/10.1002/eji.201040677.
17. Benhamron S, Tirosh B. 2011. Direct activation of mTOR in B lymphocytes confers impairment in B-cell maturation and loss of marginal zone B cells. Eur J Immunol 41:2390-2396. http://dx.doi.org/10.1002/eji.201041336.
18. Basarir T, Schwingshandl J, Borkenstein M, Rosegger H, Fueger GF. 1991. Normal values for free thyroxine, free triiodothyronine, reverse triiodothyronine, thyrotropin, thyroglobulin and thyroxine-binding globulin in umbilical cord blood of healthy mature newborn infants. Padiatr Padol 26:93-95. (In German.)
19. Byles V, Covarrubias AJ, Ben-Sahra I, Lamming DW, Sabatini DM, Manning BD, Horng T. 2013. The TSC-mTOR pathway regulates macrophage polarization. Nat Commun 4:2834. http://dx.doi.org/10.1038/ncomms3834.
20. Hu CC, Dougan SK, McGehee AM, Love JC, Ploegh HL. 2009. XBP-1 regulates signal transduction, transcription factors and bone marrow colonization in B cells. EMBO J 28:1624-1636. http://dx.doi.org/10.1038/emboj.2009.117.
21. Kang YJ, Lu MK, Guan KL. 2011. The TSC1 and TSC2 tumor suppressors are required for proper ER stress response and protect cells from ER stressinduced apoptosis. Cell Death Differ 18:133-144. http://dx.doi.org/10.1038/cdd.2010.82.
22. Moser K, Muehlinghaus G, Manz R, Mei H, Voigt C, Yoshida T, Dorner T, Hiepe F, Radbruch A. 2006. Long-lived plasma cells in immunity and immunopathology. Immunol Lett 103:83-85. http://dx.doi.org/10.1016/j.imlet.2005.09.009.
23. Tezuka H, Abe Y, Asano J, Sato T, Liu J, Iwata M, Ohteki T. 2011. Prominent role for plasmacytoid dendritic cells in mucosal T cellindependent IgA induction. Immunity 34:247-257. http://dx.doi.org/10.1016/j.immuni.2011.02.002.
24. Mijimolle N, Velasco J, Dubus P, Guerra C, Weinbaum CA, Casey PJ, Campuzano V, Barbacid M. 2005. Protein farnesyltransferase in embryogenesis, adult homeostasis, and tumor development. Cancer Cell 7:313-324. http://dx.doi.org/10.1016/j.ccr.2005.03.004.
25. Bommiasamy H, Back SH, Fagone P, Lee K, Meshinchi S, Vink E, Sriburi R, Frank M, Jackowski S, Kaufman RJ, Brewer JW. 2009. ATF6alpha induces XBP1-independent expansion of the endoplasmic reticulum. J Cell Sci 122:1626-1636. http://dx.doi.org/10.1242/jcs.045625.
26. Thuerauf DJ, Morrison LE, Hoover H, Glembotski CC. 2002. Coordination of ATF6-mediated transcription and ATF6 degradation by a domain that is shared with the viral transcription factor, VP16. J Biol Chem 277:20734-20739. http://dx.doi.org/10.1074/jbc. M201749200.
27. Wu J, Rutkowski DT, Dubois M, Swathirajan J, Saunders T, Wang J, Song B, Yau GD, Kaufman RJ. 2007. ATF6alpha optimizes long-term endoplasmic reticulum function to protect cells from chronic stress. Dev Cell 13:351-364. http://dx.doi.org/10.1016/j.devcel.2007.07.005.
28. Pengo N, Scolari M, Oliva L, Milan E, Mainoldi F, Raimondi A, Fagioli C, Merlini A, Mariani E, Pasqualetto E, Orfanelli U, Ponzoni M, Sitia R, Casola S, Cenci S. 2013. Plasma cells require autophagy for sustainable immunoglobulin production. Nat Immunol 14:298-305. http://dx.doi.org/10.1038/ni.2524.
29. Lee PY, Wang JX, Parisini E, Dascher CC, Nigrovic PA. 2013. Ly6 family proteins in neutrophil biology. J Leukoc Biol 94:585-594. http://dx.doi.org/10.1189/jlb.0113014.
30. Wrammert J, Kallberg E, Agace WW, Leanderson T. 2002. Ly6C expression differentiates plasma cells from other B cell subsets in mice. Eur J Immunol 32:97-103. http://dx.doi.org/10.1002/1521-4141(200201)32:197::AID-IMMU97 3.0.CO;2-Y.
31. Yang K, Neale G, Green DR, He W, Chi H. 2011. The tumor suppressor Tsc1 enforces quiescence of naive T cells to promote immune homeostasis and function. Nat Immunol 12:888-897. http://dx.doi.org/10.1038/ni.2068.
32. Chen H, Zhang L, Zhang H, Xiao Y, Shao L, Li H, Yin H, Wang R, Liu G, Corley D, Yang Z, Zhao Y. 2013. Disruption of TSC1/2 signaling complex reveals a checkpoint governing thymic CD4+ CD25+ Foxp3+ regulatory T-cell development in mice. FASEB J 27:3979-3990. http://dx.doi.org/10.1096/fj.13-235408.
33. Park Y, Jin HS, Lopez J, Elly C, Kim G, Murai M, Kronenberg M, Liu YC. 2013. TSC1 regulates the balance between effector and regulatory T cells. J Clin Invest 123:5165-5178. http://dx.doi.org/10.1172/JCI69751.
34. Wang Y, Huang G, Zeng H, Yang K, Lamb RF, Chi H. 2013. Tuberous sclerosis 1 (Tsc1)-dependent metabolic checkpoint controls development of dendritic cells. Proc Natl Acad Sci U S A 110:E4894-E4903. http://dx.doi.org/10.1073/pnas.1308905110.
35. Shaffer AL, Shapiro-Shelef M, Iwakoshi NN, Lee AH, Qian SB, Zhao H, Yu X, Yang L, Tan BK, Rosenwald A, Hurt EM, Petroulakis E, Sonenberg N, Yewdell JW, Calame K, Glimcher LH, Staudt LM. 2004. XBP1, downstream of Blimp-1, expands the secretory apparatus and other organelles, and increases protein synthesis in plasma cell differentiation. Immunity 21:81-93. http://dx.doi.org/10.1016/j.immuni.2004.06.010.
36. van Anken E, Romijn EP, Maggioni C, Mezghrani A, Sitia R, Braakman I, Heck AJ. 2003. Sequential waves of functionally related proteins are expressed when B cells prepare for antibody secretion. Immunity 18:243-253. http://dx.doi.org/10.1016/S1074-7613(03)00024-4.
37. Vettermann C, Castor D, Mekker A, Gerrits B, Karas M, Jack HM. 2011. Proteome profiling suggests a pro-inflammatory role for plasma cells through release of high-mobility group box 1 protein. Proteomics 11: 1228-1237. http://dx.doi.org/10.1002/pmic.201000491.
38. Srinivasan L, Sasaki Y, Calado DP, Zhang B, Paik JH, DePinho RA, Kutok JL, Kearney JF, Otipoby KL, Rajewsky K. 2009. PI3 kinase signals BCR-dependent mature B cell survival. Cell 139:573-586. http://dx.doi.org/10.1016/j.cell.2009.08.041.
39. Dowling RJ, Topisirovic I, Fonseca BD, Sonenberg N. 2010. Dissecting the role of mTOR: lessons from mTOR inhibitors. Biochim Biophys Acta 1804:433-439. http://dx.doi.org/10.1016/j.bbapap.2009.12.001.
40. Janes MR, Limon JJ, So L, Chen J, Lim RJ, Chavez MA, Vu C, Lilly MB, Mallya S, Ong ST, Konopleva M, Martin MB, Ren P, Liu Y, Rommel C, Fruman DA. 2010. Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor. Nat Med 16:205-213. http://dx.doi.org/10.1038/nm.2091.
41. Lee K, Tirasophon W, Shen X, Michalak M, Prywes R, Okada T, Yoshida H, Mori K, Kaufman RJ. 2002. IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response. Genes Dev 16:452-466. http://dx.doi.org/10.1101/gad.964702.
42. Zigmond E, Varol C, Farache J, Elmaliah E, Satpathy AT, Friedlander G, Mack M, Shpigel N, Boneca IG, Murphy KM, Shakhar G, Halpern Z, Jung S. 2012. Ly6C hi monocytes in the inflamed colon give rise to proinflammatory effector cells and migratory antigenpresenting cells. Immunity 37:1076-1090. http://dx.doi.org/10.1016/j.immuni.2012.08.026.
43. Fu S, Yang L, Li P, Hofmann O, Dicker L, Hide W, Lin X, Watkins SM, Ivanov AR, Hotamisligil GS. 2011. Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity. Nature 473:528-531. http://dx.doi.org/10.1038/nature09968.
44. Lee K, Heffington L, Jellusova J, Nam KT, Raybuck A, Cho SH, Thomas JW, Rickert RC, Boothby M. 2013. Requirement for Rictor in homeostasis and function of mature B lymphoid cells. Blood 122:2369-2379. http://dx.doi.org/10.1182/blood-2013-01-477505.
45. Keating R, Hertz T, Wehenkel M, Harris TL, Edwards BA, McClaren JL, Brown SA, Surman S, Wilson ZS, Bradley P, Hurwitz J, Chi H, Doherty PC, Thomas PG, McGargill MA. 2013. The kinase mTOR modulates the antibody response to provide cross-protective immunity to lethal infection with influenza virus. Nat Immunol 14:1266-1276. http://dx.doi.org/10.1038/ni.2741.
46. National Institutes of Health. 1985. Principles of laboratory animal care. NIH publication 85-23. National Institutes of Health, Bethesda, MD.