Abstract
Background
Historically, B cells have been considered as positive regulators of humoral immune responses. Specific B-cell subsets, however, negatively regulate immune responses and are termed “regulatory B cells” (Bregs). Recently, Bregs have been linked to not only inflammatory and autoimmune diseases, but also malignancies via suppressing antitumour immunity.
Objectives
To investigate the involvement of Bregs in advanced mycosis fungoides (MF).
Materials&Methods
The frequency ofCD19+CD24hiCD27+ memoryBcells andCD19+CD24hiCD38hi transitional B cells (which enrich IL-10-producing Bregs) was examined in peripheral blood from patients with advanced MF (n = 11) and healthy controls (n = 9) by flow cytometry. The frequency of IL-10-producing Bregs was also measured by flow cytometry. The correlation between frequency or number of B-cell subsets and disease severity markers was also analysed.
Results
The frequency of CD19+CD24hiCD27+ B cells, CD19+CD24hiCD38hi B cells, and IL-10-producing B cells was decreased in peripheral blood of advanced MF patients. The frequency and number of these B-cell subsets inversely correlated with serum soluble IL-2 receptor and serum lactate dehydrogenase levels.
Conclusions
The development of IL-10-producing Bregs is impaired in patients with advanced MF and a decrease in IL-10-producing Bregs may play an important role in the progression of advanced MF.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
LeBien TW, Tedder TF. B lymphocytes:how they develop and function. Blood 2008; 112: 1570–80.
DiLillo DJ, Matsushita T, Tedder TF. B10 cells and regulatory B cells balance immune responses during inflammation, autoimmunity, and cancer. Ann N Y Acad Sci 2010; 1183: 38–57.
Miyagaki T, Fujimoto M, Sato S. Regulatory B cells in human inflammatory and autoimmune diseases:from mouse models to clinical research. Int Immunol 2015; 27: 495–504.
Zhang Y, Gallastegui N, Rosenblatt JD. Regulatory B cells in antitumor immunity. Int Immunol 2015; 27: 521–30.
Olkhanud PB, Damdinsuren B, Bodogai M, et al. Tumor–evoked regulatory B cells promote breast cancer metastasis by converting resting CD4+ T cells to T–regulatory cells. Cancer Res 2011; 71: 3505–15.
Horikawa M, Minard–Colin V, Matsushita T, Tedder TF. Regulatory B cell production of IL–10 inhibits lymphoma depletion during CD20 immunotherapy in mice. J Clin Invest 2011; 121: 4268–80.
Qian L, Bian GR, Zhou Y, et al. Clinical significance of regulatory B cells in the peripheral blood of patients with oesophageal cancer. Cent Eur J Immunol 2015; 40: 263–5.
Wang WW, Yuan XL, Chen H, et al. CD19+CD24hiCD38hiBregs involved in downregulate helper T cells and upregulate regulatory T cells in gastric cancer. Oncotarget 2015; 6: 33486–99.
Mohr A, Renaudineau Y, Bagacean C, Pers JO, Jamin C, Bordron A. Regulatory B lymphocyte functions should be considered in chronic lymphocytic leukemia. Oncoimmunology 2016; 5:e1132977.
Willemze R, Jaffe ES, Burg G, et al. WHO–EORTC classification for cutaneous lymphomas. Blood 2005; 105: 3768–85.
Girardi M, Heald PW, Wilson LD. The pathogenesis of mycosis fungoides. N Engl J Med 2004; 350: 1978–88.
Kim EJ, Hess S, Richardson SK, et al. Immunopathogenesis and therapy of cutaneous T cell lymphoma. J Clin Invest 2005; 115: 798–812.
Blair PA, Nore˜na LY, Flores–Borja F, et al. CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic Lupus Erythematosus patients. Immunity 2010; 32: 129–40.
Iwata Y, Matsushita T, Horikawa M, et al. Characterization of a rare IL–10–competent B–cell subset in humans that parallels mouse regulatory B10 cells. Blood 2011; 117: 530–41.
Lindner S, Dahlke K, Sontheimer K, et al. Interleukin 21–induced granzyme B–expressing B cells infiltrate tumors and regulate T cells. Cancer Res 2013; 73: 2468–79.
Bankó Z, Pozsgay J, Szili D, et al. Induction and differentiation of IL–10–producing regulatory B cells from healthy blood donors and rheumatoid arthritis patients. J Immunol 2017; 198: 1512–20.
Kabasawa M, Sugaya M, Oka T, et al. Decreased interleukin–21 expression in skin and blood in advanced mycosis fungoides. J Dermatol 2016; 43: 819–22.
Shimabukuro–Vornhagen A, Schlößer HA, Gryschok L, et al. Characterization of tumor–associated B–cell subsets in patients with colorectal cancer. Oncotarget 2014; 5: 4651–64.
Chen T, Song D, Min Z, et al. Perioperative dynamic alterations in peripheral regulatory T and B cells in patients with hepatocellular carcinoma. J Transl Med 2012; 10: 14.
Jiang L, Zhan Y, Gu Y, Ye Y, Cheng Y, Shi H. Changes of regulatory T and B cells in patients with papillary thyroid carcinoma after 131I radioablation:a preliminary study. Biomed Res Int 2013; 2013: 683768.
Gjerdrum LM, Woetmann A, Odum N, et al. FOXP3+ regulatory T cells in cutaneous T–cell lymphomas:association with disease stage and survival. Leukemia 2007; 21: 2512–8.
Zhang QA, Chen ZQ, Chen MH, Xu ZD. The number of regular T cells and immature dendritic cells involved in mycosis fungoides is linked to the tumor stage. Eur Rev Med Pharmacol Sci 2014; 18: 553–8.
Krejsgaard T, Odum N, Geisler C, Wasik MA, Woetmann A. Regulatory T cells and immunodeficiency in mycosis fungoides and Sézary syndrome. Leukemia 2012; 26: 424–32.
Delfau–Larue MH, Laroche L, Wechsler J, et al. Diagnostic value of dominant T–cell clones in peripheral blood in 363 patients presenting consecutively with a clinical suspicion of cutaneous lymphoma. Blood 2000; 96: 2987–92.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Akatsuka, T., Miyagaki, T., Nakajima, R. et al. Decreased IL-10-producing regulatory B cells in patients with advanced mycosis fungoides. Eur J Dermatol 28, 314–319 (2018). https://doi.org/10.1684/ejd.2018.3319
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1684/ejd.2018.3319