Bone Marrow Mesenchymal Stem Cells Enhance the Differentiation of Human Switched Memory B Lymphocytes into Plasma Cells in Serum-Free Medium.

Guillaume Bonnaure, Catherine Gervais-St-Amour, Sonia Néron
Author Information
  1. Guillaume Bonnaure: Hema-Quebec's Department of Research and Development, 1070 Avenue des Sciences-de-la-Vie, Québec, QC, Canada G1V 5C3; Department of Biochemistry, Microbiology and Bioinformatics, Laval University, 1045 Avenue de la Médecine, Québec, QC, Canada G1V 0A6. ORCID
  2. Catherine Gervais-St-Amour: Hema-Quebec's Department of Research and Development, 1070 Avenue des Sciences-de-la-Vie, Québec, QC, Canada G1V 5C3; Department of Biochemistry, Microbiology and Bioinformatics, Laval University, 1045 Avenue de la Médecine, Québec, QC, Canada G1V 0A6.
  3. Sonia Néron: Hema-Quebec's Department of Research and Development, 1070 Avenue des Sciences-de-la-Vie, Québec, QC, Canada G1V 5C3; Department of Biochemistry, Microbiology and Bioinformatics, Laval University, 1045 Avenue de la Médecine, Québec, QC, Canada G1V 0A6. ORCID

Abstract

The differentiation of human B lymphocytes into plasma cells is one of the most stirring questions with regard to adaptive immunity. However, the terminal differentiation and survival of plasma cells are still topics with much to be discovered, especially when targeting switched memory B lymphocytes. Plasma cells can migrate to the bone marrow in response to a CXCL12 gradient and survive for several years while secreting antibodies. In this study, we aimed to get closer to niches favoring plasma cell survival. We tested low oxygen concentrations and coculture with mesenchymal stem cells (MSC) from human bone marrow. Besides, all cultures were performed using an animal protein-free medium. Overall, our model enables the generation of high proportions of CD38CD138CD31 plasma cells (≥50%) when CD40-activated switched memory B lymphocytes were cultured in direct contact with mesenchymal stem cells. In these cultures, the secretion of CXCL12 and TGF-, usually found in the bone marrow, was linked to the presence of MSC. The level of oxygen appeared less impactful than the contact with MSC. This study shows for the first time that expanded switched memory B lymphocytes can be differentiated into plasma cells using exclusively a serum-free medium.

References

  1. J Immunol. 2010 Dec 15;185(12):7180-5 [PMID: 21068399]
  2. ScientificWorldJournal. 2013 Aug 27;2013:632972 [PMID: 24068884]
  3. Leukemia. 2014 Aug;28(8):1647-56 [PMID: 24504026]
  4. Immunity. 2000 Oct;13(4):443-51 [PMID: 11070163]
  5. Blood. 2008 Mar 1;111(5):2755-64 [PMID: 18180376]
  6. J Exp Med. 2004 Nov 1;200(9):1145-56 [PMID: 15520246]
  7. J Immunol Methods. 2011 Aug 31;371(1-2):61-9 [PMID: 21723869]
  8. Immunity. 2013 Jul 25;39(1):136-47 [PMID: 23850379]
  9. J Immunol Res. 2014;2014:635108 [PMID: 25759831]
  10. EMBO Rep. 2006 Sep;7(9):880-5 [PMID: 16953201]
  11. Immunology. 2005 Dec;116(4):454-63 [PMID: 16313359]
  12. Transfusion. 2007 Jun;47(6):1042-9 [PMID: 17524095]
  13. Cytometry A. 2014 Jan;85(1):43-77 [PMID: 24700575]
  14. Protein Cell. 2011 Oct;2(10):845-54 [PMID: 22058039]
  15. Blood. 2010 Sep 16;116(11):1867-75 [PMID: 20538807]
  16. J Immunol. 2003 Aug 15;171(4):1684-90 [PMID: 12902466]
  17. J Immunol. 2015 Oct 15;195(8):3716-24 [PMID: 26355154]
  18. Cell Transplant. 2013;22(2):369-79 [PMID: 23433427]
  19. J Immunol. 2002 Aug 1;169(3):1277-82 [PMID: 12133949]
  20. Nat Biotechnol. 2011 Oct 02;29(10):886-91 [PMID: 21964415]
  21. Neurobiol Dis. 2012 Jun;46(3):635-45 [PMID: 22426403]
  22. Science. 2012 Jan 20;335(6066):342-4 [PMID: 22174128]
  23. Immunol Rev. 2010 Sep;237(1):140-59 [PMID: 20727034]
  24. Immunity. 2004 Jun;20(6):707-18 [PMID: 15189736]
  25. J Immunol. 2008 Mar 15;180(6):3655-9 [PMID: 18322170]
  26. J Immunother. 2007 Jul-Aug;30(5):567-76 [PMID: 17589298]
  27. J Immunol. 2012 Dec 15;189(12):5773-85 [PMID: 23162129]
  28. Blood. 2009 Aug 13;114(7):1340-3 [PMID: 19571319]
  29. FEBS Lett. 2007 Jul 31;581(19):3652-7 [PMID: 17475256]
  30. Stem Cells. 2007 Jul;25(7):1603-9 [PMID: 17395775]
  31. Mol Immunol. 2014 Nov;62(1):209-18 [PMID: 25016575]
  32. J Immunol. 2008 Jun 15;180(12):8153-8 [PMID: 18523280]
  33. J Cell Physiol. 2010 Jan;222(1):17-22 [PMID: 19725055]
  34. J Exp Med. 2011 Jul 4;208(7):1435-46 [PMID: 21690252]
  35. Bone Marrow Transplant. 2009 Oct;44(8):457-62 [PMID: 19861978]
  36. Nature. 2014 Jan 16;505(7483):327-34 [PMID: 24429631]
  37. J Immunol. 2012 Feb 1;188(3):1283-91 [PMID: 22262758]
  38. J Immunol. 2008 Jan 1;180(1):361-71 [PMID: 18097037]
  39. Stem Cells Dev. 2014 Nov 1;23(21):2591-9 [PMID: 24937591]
  40. Cell Immunol. 2015 Jun;295(2):127-36 [PMID: 25880104]
  41. Immunol Invest. 1996 Jan-Mar;25(1-2):79-89 [PMID: 8675236]
  42. Immunity. 2009 May;30(5):721-30 [PMID: 19427242]
  43. Front Immunol. 2012 Jul 20;3:212 [PMID: 22833744]
  44. Eur J Immunol. 2012 Jan;42(1):130-7 [PMID: 22057654]
  45. Adv Exp Med Biol. 2007;602:69-75 [PMID: 17966390]
  46. Nat Rev Immunol. 2015 Mar;15(3):160-71 [PMID: 25698678]
  47. Clin Exp Immunol. 2010 Jul 1;161(1):176-86 [PMID: 20456409]
  48. Eur J Immunol. 1986 Feb;16(2):139-45 [PMID: 2869953]
  49. Stem Cells. 2008 Feb;26(2):562-9 [PMID: 18024418]
  50. Cell. 2015 Jun 18;161(7):1553-65 [PMID: 26073944]
  51. Eur J Immunol. 2014 Aug;44(8):2306-17 [PMID: 24777940]
  52. PLoS One. 2012;7(10):e46772 [PMID: 23071634]
  53. Cytokine. 2011 Feb;53(2):184-90 [PMID: 20609598]
  54. Cytotherapy. 1999;1(6):455-68 [PMID: 20426546]
  55. Nat Commun. 2011 Sep 06;2:465 [PMID: 21897376]
  56. Nat Rev Immunol. 2003 Oct;3(10):822-9 [PMID: 14523388]
  57. J Hematother Stem Cell Res. 2001 Dec;10(6):873-80 [PMID: 11798513]
  58. PLoS One. 2013 Nov 14;8(11):e79283 [PMID: 24244468]
  59. J Clin Invest. 2011 May;121(5):1946-55 [PMID: 21490392]
  60. PLoS Comput Biol. 2015 Jan 29;11(1):e1004077 [PMID: 25633866]
  61. Biol Blood Marrow Transplant. 2016 Feb;22(2):359-70 [PMID: 26409243]
  62. Blood. 2015 Nov 26;126(22):2443-51 [PMID: 26468230]
  63. Stem Cell Res Ther. 2014 Apr 16;5(2):53 [PMID: 24739658]
  64. Stem Cells. 2006 Feb;24(2):386-98 [PMID: 16123384]
  65. Nat Rev Immunol. 2015 Mar;15(3):149-59 [PMID: 25677494]
  66. J Clin Invest. 2003 Jul;112(2):286-97 [PMID: 12865416]
  67. J Exp Med. 2000 Sep 18;192(6):813-21 [PMID: 10993912]
  68. J Cell Biochem. 2009 Oct 15;108(3):577-88 [PMID: 19650110]
  69. Scand J Immunol. 2007 Apr;65(4):336-43 [PMID: 17386024]
  70. Immunity. 2015 Jul 21;43(1):132-45 [PMID: 26187412]
  71. Immunol Rev. 2013 Jan;251(1):177-88 [PMID: 23278749]
  72. Trends Immunol. 2011 Dec;32(12):595-602 [PMID: 22001488]
  73. Science. 2012 Jan 20;335(6066):338-41 [PMID: 22223740]
  74. PLoS One. 2012;7(12):e51946 [PMID: 23284827]
  75. Immunology. 2009 Sep;128(1 Suppl):e353-65 [PMID: 19016905]
  76. ALTEX. 2010;27(1):53-62 [PMID: 20390239]
  77. Nat Immunol. 2011 Feb;12(2):151-9 [PMID: 21217761]
  78. J Immunol. 2006 Sep 15;177(6):3728-36 [PMID: 16951333]
  79. Cytotherapy. 2016 Jan;18(1):13-24 [PMID: 26631828]
  80. Nat Immunol. 2011 May;12(5):391-8 [PMID: 21441933]
  81. Arch Immunol Ther Exp (Warsz). 2011 Feb;59(1):25-40 [PMID: 21234809]
  82. Cell Mol Life Sci. 2016 Feb;73(4):687-703 [PMID: 26495446]
  83. Blood. 2010 Jul 22;116(3):375-85 [PMID: 20393133]
  84. World J Stem Cells. 2014 Nov 26;6(5):552-70 [PMID: 25426252]
  85. Blood. 2009 Feb 5;113(6):1250-6 [PMID: 18945958]

MeSH Term

B-Lymphocytes
Biomarkers
CD40 Antigens
Cell Differentiation
Cells, Cultured
Culture Media, Serum-Free
Cytokines
Humans
Immunologic Memory
Immunophenotyping
Lymphocyte Activation
Mesenchymal Stem Cells
Oxidation-Reduction
Oxygen
Plasma Cells

Chemicals

Biomarkers
CD40 Antigens
Culture Media, Serum-Free
Cytokines
Oxygen

Word Cloud

Created with Highcharts 10.0.0cellsBplasmalymphocytesswitchedmemorybonemarrowMSCdifferentiationhumansurvivalPlasmacanCXCL12studyoxygenmesenchymalstemculturesusingmediumcontactCellsonestirringquestionsregardadaptiveimmunityHoweverterminalstilltopicsmuchdiscoveredespeciallytargetingmigrateresponsegradientsurviveseveralyearssecretingantibodiesaimedgetclosernichesfavoringcelltestedlowconcentrationscocultureBesidesperformedanimalprotein-freeOverallmodelenablesgenerationhighproportionsCD38CD138CD31≥50%CD40-activatedcultureddirectsecretionTGF-usuallyfoundlinkedpresencelevelappearedlessimpactfulshowsfirsttimeexpandeddifferentiatedexclusivelyserum-freeBoneMarrowMesenchymalStemEnhanceDifferentiationHumanSwitchedMemoryLymphocytesSerum-FreeMedium

Similar Articles

Cited By