Advertisement

Neurological Sciences

, Volume 38, Issue 7, pp 1205–1212 | Cite as

Circulating regulatory B cell subsets in patients with neuromyelitis optica spectrum disorders

  • Jinming Han
  • Li Sun
  • Zhongkun Wang
  • Xueli Fan
  • Lifang Wang
  • Yang-yang Song
  • Jie Zhu
  • Tao JinEmail author
Original Article

Abstract

This study analyzed the populations of three different subsets of regulatory B cells (Bregs) in the peripheral blood mononuclear cells (PBMCs) of patients with neuromyelitis optica spectrum disorders (NMOSDs) and explored the relationship between the changes in these subsets of Bregs and the severity of NMOSD. A total of 22 patients with relapsed NMOSDs before treatment were recruited in our study, along with 20 age and gender-matched healthy controls, from May 2015 to March 2016. The percentages and numbers for three different subsets of Bregs including the CD19+CD24hiCD38hi, CD19+CD24hiCD27+, and CD19+CD5+CD1dhi populations were evaluated in parallel by flow cytometry. Afterwards, correlations between the change of three different subsets of Bregs and disease severity were analyzed. We found significantly lower percentages of CD19+CD24hiCD38hi and CD19+CD5+CD1dhi Bregs in NMOSDs patients than in healthy individuals. In contrast, the CD19+CD24hiCD27+ Bregs population was significantly higher in NMOSDs patients than in healthy individuals. However, the three different Bregs subsets showed no significant correlation with expanded disability status scale (EDSS) or annualized relapse rate (ARR). Our findings suggest that the subsets of Bregs may play complex roles in the pathogenesis of NMOSDs and are not correlated with clinical disease severity. Further insights into the potential role of subsets of Bregs could increase our basic knowledge of NMOSDs pathogenesis.

Keywords

Regulatory B cells (Bregs) Neuromyelitis optica spectrum disorders (NMOSDs) Flow cytometry 

Notes

Acknowledgments

This work was supported by grants from the General Program of the National Natural Science Foundation of China (Nos. 81671177 and 81471216), the International Science and Technology Cooperation Program of Jilin Provincial Science and Technology Development of China (No. 20150414011GH), the Norman Bethune Cultivation Plan of Jilin University (No. 2015320), the Science and Technology Program of Jilin Provincial Education Department of China (No. 2016-462), as well as the grants from the Swedish Research Council (K2013-66X-22337-01-3 and project number 2015-03005) and grants from the First Hospital, Jilin University of China.

Compliance with ethical standards

Conflict of interest

The authors report that they have no conflict of interest.

Supplementary material

10072_2017_2932_Fig5_ESM.gif (12 kb)
Figure S1

(GIF 12 kb).

10072_2017_2932_MOESM1_ESM.tif (5.5 mb)
High resolution image (TIFF 5584 kb).
10072_2017_2932_Fig6_ESM.gif (38 kb)
Figure S2

(GIF 37 kb).

10072_2017_2932_MOESM2_ESM.tif (15.1 mb)
High resolution image (TIFF 15445 kb).

References

  1. 1.
    Jasiak-Zatonska M, Kalinowska-Lyszczarz A, Michalak S, Kozubski W (2016) The immunology of neuromyelitis optica—current knowledge, clinical implications, controversies and future perspectives. Int J Mol Sci 17(3):273CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, de Seze J, Fujihara K, Greenberg B, Jacob A, Jarius S, Lana-Peixoto M, Levy M, Simon JH, Tenembaum S, Traboulsee AL, Waters P, Wellik KE, Weinshenker BG (2015) N.M.O.D. International panel for, International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 85(2):177–189CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Krumbholz M, Meinl E (2014) B cells in MS and NMO: pathogenesis and therapy. Semin Immunopathol 36(3):339–350CrossRefPubMedGoogle Scholar
  4. 4.
    Bennett JL, O’Connor KC, Bar-Or A, Zamvil SS, Hemmer B, Tedder TF, von Budingen HC, Stuve O, Yeaman MR, Smith TJ, Stadelmann C (2015) B lymphocytes in neuromyelitis optica. Neurology(R) neuroimmunology & neuroinflammation 2(3):e104CrossRefGoogle Scholar
  5. 5.
    Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, Nakashima I, Weinshenker BG (2004) A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 364(9451):2106–2112CrossRefPubMedGoogle Scholar
  6. 6.
    Egwuagu CE, Yu CR (2015) Interleukin 35-producing B cells (i35-Breg): a new mediator of regulatory B-cell functions in CNS autoimmune diseases. Crit Rev Immunol 35(1):49–57CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Kalampokis I, Yoshizaki A, Tedder TF (2013) IL-10-producing regulatory B cells (B10 cells) in autoimmune disease. Arthritis Res Ther 15(Suppl 1):S1CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Lee KM, Stott RT, Zhao G, SooHoo J, Xiong W, Lian MM, Fitzgerald L, Shi S, Akrawi E, Lei J, Deng S, Yeh H, Markmann JF, Kim JI (2014) TGF-beta-producing regulatory B cells induce regulatory T cells and promote transplantation tolerance. Eur J Immunol 44(6):1728–1736CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Han J, Sun L, Fan X, Wang Z, Cheng Y, Zhu J, Jin T (2016) Role of regulatory b cells in neuroimmunologic disorders. J Neurosci Res 94(8):693–701CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Correale J, Farez M, Razzitte G (2008) Helminth infections associated with multiple sclerosis induce regulatory B cells. Ann Neurol 64(2):187–199CrossRefPubMedGoogle Scholar
  11. 11.
    Blair PA, Norena LY, Flores-Borja F, Rawlings DJ, Isenberg DA, Ehrenstein MR, Mauri C (2010) CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic lupus erythematosus patients. Immunity 32(1):129–140CrossRefPubMedGoogle Scholar
  12. 12.
    Iwata Y, Matsushita T, Horikawa M, Dilillo DJ, Yanaba K, Venturi GM, Szabolcs PM, Bernstein SH, Magro CM, Williams AD, Hall RP, Clair EWS, Tedder TF (2011) Characterization of a rare IL-10-competent B-cell subset in humans that parallels mouse regulatory B10 cells. Blood 117(2):530–541CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    de Andres C, Tejera-Alhambra M, Alonso B, Valor L, Teijeiro R, Ramos-Medina R, Mateos D, Faure F, Sanchez-Ramon S (2014) New regulatory CD19(+)CD25(+) B-cell subset in clinically isolated syndrome and multiple sclerosis relapse. Changes after glucocorticoids. J Neuroimmunol 270(1–2):37–44CrossRefPubMedGoogle Scholar
  14. 14.
    Knippenberg S, Peelen E, Smolders J, Thewissen M, Menheere P, Cohen Tervaert JW, Hupperts R, Damoiseaux J (2011) Reduction in IL-10 producing B cells (Breg) in multiple sclerosis is accompanied by a reduced naive/memory Breg ratio during a relapse but not in remission. J Neuroimmunol 239(1–2):80–86CrossRefPubMedGoogle Scholar
  15. 15.
    Michel L, Chesneau M, Manceau P, Genty A, Garcia A, Salou M, Elong Ngono A, Pallier A, Jacq-Foucher M, Lefrere F, Wiertlewski S, Soulillou JP, Degauque N, Laplaud DA, Brouard S (2014) Unaltered regulatory B-cell frequency and function in patients with multiple sclerosis. Clin Immunol 155(2):198–208CrossRefPubMedGoogle Scholar
  16. 16.
    Quan C, Yu H, Qiao J, Xiao B, Zhao G, Wu Z, Li Z, Lu C (2013) Impaired regulatory function and enhanced intrathecal activation of B cells in neuromyelitis optica: distinct from multiple sclerosis. Mult Scler 19(3):289–298CrossRefPubMedGoogle Scholar
  17. 17.
    Yang F, Huang D, Cheng C, Wu W (2015) Proportion and significance of CD1d(hi)CD5(+)CD19(+) regulatory B cell in peripheral blood of patients with neuromyelitis optica. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 31(3):375–378PubMedGoogle Scholar
  18. 18.
    Zha B, Wang L, Liu X, Liu J, Chen Z, Xu J, Sheng L, Li Y, Chu Y (2012) Decrease in proportion of CD19+ CD24(hi) CD27+ B cells and impairment of their suppressive function in Graves’ disease. PLoS One 7(11):e49835CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Mavropoulos A, Simopoulou T, Varna A, Liaskos C, Katsiari CG, Bogdanos DP, Sakkas LI (2016) Breg cells are numerically decreased and functionally impaired in patients with systemic sclerosis. Arthritis Rheumatol 68(2):494–504CrossRefPubMedGoogle Scholar
  20. 20.
    Daien CI, Gailhac S, Mura T, Audo R, Combe B, Hahne M, Morel J (2014) Regulatory B10 cells are decreased in patients with rheumatoid arthritis and are inversely correlated with disease activity. Arthritis Rheumatol 66(8):2037–2046CrossRefPubMedGoogle Scholar
  21. 21.
    Todd SK, Pepper RJ, Draibe J, Tanna A, Pusey CD, Mauri C, Salama AD (2014) Regulatory B cells are numerically but not functionally deficient in anti-neutrophil cytoplasm antibody-associated vasculitis. Rheumatology 53(9):1693–1703CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Barsotti NS, Almeida RR, Costa PR, Barros MT, Kalil J, Kokron CM (2016) IL-10-producing regulatory B cells are decreased in patients with common variable immunodeficiency. PLoS One 11(3):e0151761CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Italia 2017

Authors and Affiliations

  1. 1.Department of Neurology and Neuroscience Centerthe First Hospital of Jilin UniversityChangchunChina
  2. 2.Department of Neurobiology, Care Sciences and SocietyKarolinska InstituteStockholmSweden

Personalised recommendations