Regulatory B Cells and Role in Cancer

Year 2020, Volume: 10 Issue: 2, 326 - 333, 15.06.2020

Berna Erdal , Bahar Yılmaz

https://doi.org/10.31832/smj.711179

Abstract

B cells, the humoral immune response element, are the cells responsible for antibody production. Progenitor B cells, mature in bone marrow. The surface of B cells contains antigen receptors, immunoglobulin receptors, adhesion molecules and Major Histocompatibility Complex (MHC) molecules. The development of the ability of these cells to bind antigen occurs depending on T cells in secondary lymphoid organs and in the specific microenvironment of lymph follicles. As a result of an antigenic stimulation, activated B cells differentiate into plasma cells or memory B cells. Regulatory B (Breg) cells, a subset of B cells, are immunosuppressive cells that support immunological tolerance. Interleukin (IL)-10, IL-35, and transforming growth factor beta (TGF-β) producing Breg cells inhibit autoimmune pathology by preventing the expression of T cells and other pro-inflammatory lymphocytes. Recent studies have shown that different inflammatory environments induce different Breg cell populations. Various Breg subsets have been identified in inflammation, transplantation and autoimmunity models in both humans and animals. In this review, it is aimed to provide an overview of the developmental origin, phenotype, subsets, functions and roles in cancer of Breg cells.

Keywords

Regulatory B Cell, Interleukin-10, Cancer

Düzenleyici B Hücreleri ve Kanserdeki Rolü

Abstract

Hümoral immün yanıt elemanı olan B hücreleri antikor üretiminden sorumlu hücrelerdir. Progenitör B hücreleri, kemik iliğinde olgunlaşırlar. B hücrelerinin yüzeyinde antijen reseptörleri, immünglobulin reseptörleri, adhezyon molekülleri ve Major Doku Uygunluk Kompleksin (MHC) molekülleri bulunur. Bu hücrelerin antijene bağlanma yeteneğinin gelişmesi sekonder lenfoid organlarda ve lenf foliküllerinin kendine özgü mikroçevresinde, T hücrelerine bağımlı olarak gerçekleşmektedir. Antijenik bir uyarım sonucunda aktive olan B hücreleri plazma hücrelerine veya bellek B hücrelerine farklılaşırlar. Düzenleyici B (Breg) hücreleri, immünolojik toleransı destekleyen B hücrelerinin alt grubu olan immünsüpresif hücrelerdir. İnterlökin-10 (IL-10), IL-35 ve transforme edici büyüme faktörü beta (TGF-β) üreten Breg hücreleri, T hücrelerin ve diğer pro-enflamatuar lenfositlerin ifadesini engelleyerek otoimmün patolojiyi baskılar. Son çalışmalar, farklı enflamatuar ortamların farklı Breg hücre popülasyonlarını uyardığını göstermiştir. Hem insanlarda hem de hayvanlarda enflamasyon, transplantasyon ve otoimmünite modellerinde çeşitli Breg alt grupları tanımlanmıştır. Bu derlemede, Breg hücrelerinin gelişimsel kökenine, fenotipine, alt gruplarına, işlevlerine ve kanserdeki rollerine genel bir bakış sunulması amaçlanmaktadır.

Keywords

Düzenleyici B Hücre, İnterlökin-10, Kanser

References

• You Chao D, Jıxın Z, Jun-Fa X. Regulatory B Cells İn İnfectious Disease. Molecular Medıcıne Reports 2017; 16: 3-10.
• Rowa Y. A, Estefanía N, Octavio A, Hannah M. B, Robert I. L, Anthony D, Giovanna L. Regulatory B cells: Development, phenotypes, functions, and role in transplantation. Immunological Reviews 2019; 00: 1–16.
• Rosser EC, Mauri C. Regulatory B cells: origin, phenotype, and function. Immunity 2015; 42(4): 607‐612.
• Mauri C, Bosma A. Immune regulatory function of B cells. Annu Rev Immunol. 2012; 30: 221‐241.
• D.C. Fitzgerald, G.-X. Zhang, M. El-Behi, Z. Fonseca-Kelly, H. Li, S. Yu, C.J. Saris, B. Gran, B. Ciric, A. Rostami, Suppression of autoimmune inflammation of the central nervous system by interleukin 10 secreted by interleukin 27–stimulated T cells, Nat. Immunol. 2007; 8(12): 1372-1379.
• Medzhitov R. Origin and physiological roles of inflammation. Nature 2008; 454: 428–435.
• Nathan C, Ding A. Nonresolving inflammation. Cell 2010; 140: 871–882.
• Maynard C.L, Weaver C.T. Diversity in the contribution of interleukin‐10 to T‐cell‐mediated immune regulation. Immunol. Rev. 2008; 226(1): 219–233.
• Saraiva M, Christensen J.R, Veldhoen M, Murphy T.L, Murphy K.M, O’Garra A. Interleukin-10 production by Th1 cells requires interleukin-12-induced STAT4 transcription factor and ERK MAP kinase activation by high antigen dose. Immunity 2009; 31(2): 209–219.
• Gilliet M, Liu Y.J. Generation of human CD8 T regulatory cells by CD40 ligand activated plasmacytoid dendritic cells. J. Exp. Med. 2002; 195(6): 695–704.
• Grimbaldeston M.A, Nakae S, Kalesnikoff J, Tsai M, Galli S.J. Mast cell–derived interleukin 10 limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B. Nat. Immunol. 2007; 8(10): 1095.
• Moore K.W, de Waal Malefyt R, Coffman R.L, O’Garra A. Interleukin-10 and the interleukin-10 receptor. Annu. Rev. Immunol. 2001; 19(1): 683–765.
• Blair P.A, Noreña L.Y, Flores-Borja F, Rawlings D.J, Isenberg D.A, Ehrenstein M.R, Mauri C, CD19+CD24hiCD38hi B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic lupus erythematosus patients. Immunity 2010; 32(1): 129–140.
• Iwata Y, Matsushita T, Horikawa M, DiLillo D.J, Yanaba K, Venturi G.M, Szabolcs P.M, Bernstein S.H, Magro C.M, Williams A.D. Characterization of a rare IL-10 competent B-cell subset in humans that parallels mouse regulatory B10 cells. Blood 2011; 117(2): 530–541.
• McGeachy M.J, Bak-Jensen K.S, Chen Y, Tato C.M, Blumenschein W, McClanahan T, Cua D.J. TGF-β and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T H-17 cell–mediated pathology. Nat. Immunol. 2007; 8(12): 1390-1397.
• Stumhofer J.S, Silver J.S, Laurence A, Porrett P.M, Harris T.H, Turka L.A, Ernst M, Saris C.J, O’Shea J.J, Hunter C.A. Interleukins 27 and 6 induce STAT3 mediated T cell production of interleukin 10. Nat. Immunol. 2007; 8(12): 1363-1371.
• Delves PJ, Roitt IM. The immune system. First of two parts. N Engl J Med. 2000; 6,343(1): 37-49.
• Öztürk E. B hücre aktivasyonu ve antikor üretimi. Türkdem 2013; 47:Özel Sayı 1: 24-7.
• Mizoguchi A, Mizoguchi E, Takedatsu H, Blumberg R.S, Bhan A.K. Chronic intestinal inflammatory condition generates IL-10-producing Immunity Perspective regulatory B cell subset characterized by CD1d upregulation. Immunity 2002; 16: 219–230.
• Yaz İ. Yaygın Değişken İmmün Yetmezlik Hastalarının Klinik, İmmünolojik Ve Genetik Özelliklerinin B Hücre Alt Grup Özellikleri Ve Krec Sayıları İle Korelasyonunun Araştırılması, Hacettepe Üniversitesi Sağlık Bilimleri Enstitüsü İmmünoloji Programı. Yüksek Lisans Tezi. 2019; Ankara.
• İlhan F, Taş S.K. Organ Nakillerinde Regülatör B Hücrelerin Rolü. Turkiye Klinikleri J Immun Allergy-Special Topics 2013; 6(2): 29-35.
• Adams AB, Newell KA. B cells in clinical transplantation tolerance. Semin Immunol. 2012; 24 (2): 92-5.
• Duddy ME, Alter A, Bar-Or A. Distinct profiles of human B cell effector cytokines: a role in immune regulation. J Immunol. 2004; 172(6): 3422-3427.
• Wortel CM, Heidt S. Regulatory B cells: Phenotype, function and role in transplantation. Transplant Immunology 2017; 41: 1–9.
• Valizadeh A, Sanaeib R, Rezaeia N, Azizid G, Fekrvanda S, Aghamohammadia A, Yazdania R. Potential role of regulatory B cells in immunological diseases. Immunology Letters 2019; 215: 48–59.
• Carter N.A, Vasconcellos R, Rosser E.C, Tulone C, Muñoz-Suano A, Kamanaka M, Ehrenstein M.R, Flavell R.A, Mauri C. Mice lacking endogenous IL-10–producing regulatory B cells develop exacerbated disease and present with an increased frequency of Th1/Th17 but a decrease in regulatory T cells. J. Immunol. 2011; 186(10): 5569–5579.
• Gray M, Miles K, Salter D, Gray D, Savill J. Apoptotic cells protect mice from autoimmune inflammation by the induction of regulatory B cells, Proc. Natl. Acad. Sci. U. S. A. 2007; 104 (35): 14080–14085.
• Zhang X, Deriaud E, Jiao X, Braun D, Leclerc C, Lo-Man R. Type I interferons protect neonates from acute inflammation through interleukin 10–producing B cells. J. Exp. Med. 2007; 204(5): 1107–1118.
• Lundy S.K, Fox D.A. Reduced Fas ligand-expressing splenic CD5+ B lymphocytes in severe collagen-induced arthritis. Arthritis Res. Ther. 2009; 11(4): R128.
• Khoder A, Sarvaria A, Alsuliman A, Chew C, Sekine T, Cooper N, Mielke S, De Lavallade H, Muftuoglu M, Curbelo I.F. Regulatory B cells are enriched within the IgM memory and transitional subsets in healthy donors but are deficient in chronic GVH. Blood. 2014; 124(13): 2034–2045.
• Lino A.C, Lampropoulou V, Welle A, Joedicke J, Pohar J, Simon Q, Thalmensi J, Baures A, Flühler V, Sakwa I. LAG-3 inhibitory receptor expression identifies immunosuppressive natural regulatory plasma cells. Immunity 2018; 49(1): 120–133.
• Ding Q, Yeung M, Camirand G, Zeng Q, Akiba H, Yagita H, Chalasani G, Sayegh M.H, Najafian N, Rothstein D.M. Regulatory B cells are identified by expression of TIM-1 and can be induced through TIM-1 ligation to promote tol- erance in mice. J. Clin. Invest. 2011; 121(9): 3645-3656.
• Matsumoto M, Baba A, Yokota T, Nishikawa H, Ohkawa Y, Kayama H, Kallies A, Nutt S.L, Sakaguchi S, Takeda K. Interleukin-10-producing plasmablasts exert regulatory function in autoimmune inflammation. Immunity 2014; 41(6): 1040–1051.
• Lindner S, Dahlke K, Sontheimer K, Hagn M, Kaltenmeier C, Barth T.F, Beyer T, Reister F, Fabricius D, Lotfi R. Interleukin 21–induced granzyme B–expressing B cells infiltrate tumors and regulate T cells. Cancer Res. 2013; 73(8): 2468–2479.
• Van de Veen W, Stanic B, Yaman G, Wawrzyniak M, Söllner S, Akdis D.G, Rückert B, Akdis C, Akdis M. IgG4 production is confined to human IL10–producing regulatory B cells that suppress antigen-specific immune responses. J. Allergy Clin. Immunol. 2013; 131(4): 1204–1212.
• Rafei M, Hsieh J, Zehntner S, Li M, Forner K, Birman E, Boivin M.N, Young Y.K, Perreault C, Galipeau J. A granulocyte-macrophage colony–stimulating factor and interleukin-15 fusokine induces a regulatory B cell population with immune suppressive properties. Nat. Med. 2009; 15(9): 1038-1045.
• A.R. Khan, E. Hams, A. Floudas, T. Sparwasser, C.T. Weaver, P.G. Fallon, PD-L1hi B cells are critical regulators of humoral immunity, Nat. Commun. 2015; 6: 5997.
• Watanabe R, Ishiura N, Nakashima H, Kuwano Y, Okochi H, Tamaki K. Regulatory B cells (B10 cells) have a suppressive role in murine lupus: CD19 and B10 cell deficiency exacerbates systemic autoimmunity. J. Immunol. 2010; 184(9): 4801–4809.
• Kalampokis I, Yoshizaki A, Tedder T.F. IL-10-producing regulatory B cells (B10 cells) in autoimmune disease. Arthritis Res. Ther. 2013; 15(1): S1.
• Xiao S, Brooks C.R, Sobel R.A, Kuchroo V.K. Tim-1 is essential for induction and maintenance of IL-10 in regulatory B cells and their regulation of tissue inflammation. J. Immunol. 2015; 194(4): 1602–1608.
• Gasperi C, Melms A, B Schoser, Zhang Y, Meltoranta J, Risson V, Schaeffer L, Schalke B, Kröger S. Anti-agrin autoantibodies in myasthenia gravis. Neurology 2014; 82(22): 1976–1983.
• Sayi A, Kohler E, Toller I.M, Flavell R.A, Muller W, Roers A, Müller A. TLR-2-activated B cells suppress Helicobacter-induced preneoplastic gastric immunopathology by inducing T regulatory-1 cells. J Immunol. 2011; 186: 878-890.
• Chesneau M, Michel L, Dugast E, Chenouard A, Baron D, Pallier A. Tolerant kidney transplant patients produce B cells with regulatory properties. J. Am. Soc. Nephrol. 2015; 26(10): 2588–2598.
• Zeng Q, Ng Y.H, Singh T, Jiang K, Sheriff K.A, Ippolito R. B cells mediate chronic allograft rejection independently of antibody production. J. Clin. Invest. 2014; 124(3): 1052–1056.
• Maseda D, Smith S.H, DiLillo D.J, Bryant J.M, Candando K.M, Weaver C.T. Regulatory B10 cells differentiate into antibody-secreting cells after transient IL-10 production in vivo. J. Immunol. 2012; 188(3): 1036–1048.
• Deng S, Moore D.J, Huang X, Lian M.M, Mohiuddin M, Velededeoglu E. Cutting edge: transplant tolerance induced by anti-CD45RB requires B lymphocytes. J. Immunol. 2007; 178 (10): 6028–6032.
• Tarique M, Naz H, Kurra S.V, Naqvi R.A, Saini C, Rai R, Suhail M, Khanna N, Rao D.N, Sharma A.J.F. IL-10-producing regulatory B cells transformed CD4+CD25- into Tregs and enhanced regulatory T cells function in human leprosy. Front. Immunol. 2018; 9: ID1636.
• Zhao Y, Shen M, Feng Y, He R, Xu X, Xie Y, Shi X, Zhou M, Pan S, Wang M, Guo X, Qin R. Regulatory B cells induced by pancreatic cancer cell-derived interleukin-18 promote immune tolerance via the PD-1/PD-L1 pathway. Oncotarget 2018; 9(19): 14803-14814.
• Lee-Chang C, Bodogai M, Martin-Montalvo A, Wejksza K, Sanghvi M, Moaddel De Cabo R, Biragyn R. Inhibition of breast cancer metastasis by resveratrol-mediated inactivation of tumor-evoked regulatory B cells, J. Immunol. 2013; 191(8): 4141–4151.
• Mehdipour F, Razmkhah M, Hosseini A, Bagheri M, Safaei A, Talei A.R, Ghaderi A. Increased B regulatory phenotype in non‐metastatic lymph nodes of node‐positive breast cancer patients. Scand. J. Immunol. 2016; 83(3): 195–202.
• Lee-Chang C, Bodogai M, Martin-Montalvo A, Wejksza K, Sanghvi M, Moaddel R, de Cabo R, Biragyn A. Inhibition of Breast Cancer Metastasis by Resveratrol-Mediated Inactivation of Tumor-Evoked Regulatory B Cells J Immunol. 2013; 191(8): 4141-4151.
• Ferlay J, Shin H.R, Bray F, Forman D, Mathers C, Parkin D.M. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008, Int. J. Cancer 2010; 127(12): 2893–2917.
• Shi J, Li S, Zhou Y, Wang L, Wen J, Wang Y, Kang Z. Perioperative changes in peripheral regulatory B cells of patients with esophageal cancer. Mol. Med. Rep. 2014; 10(3): 1525–1530.
• Aravalli R.N, Cressman E.N, Steer C.J. Cellular and molecular mechanisms of hepatocellular carcinoma: an update. Arch. Toxicol. 2013; 87(2): 227–247.
• Shao Y, Lo C.M, C Ling.C, Liu X.B, Ng K.T.-P, Chu A.C.Y, Ma Y.Y, Li C.X, Fan S.T, Man K. Regulatory B cells accelerate hepatocellular carcinoma progression via CD40/CD154 signaling pathway, Cancer Lett. 2014; 355(2): 264–272.
• Meucci S, Keilholz U, Tinhofer I, Ebner OA. Mutational load and mutational patterns in relation to age in head and neck cancer. Oncotarget 2016; 7: 69188–69199.
• Ferris RL, Blumenschein G Jr, Fayette J. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 2016; 375: 1856–1867.
• Jeske S.S, Brand M, Ziebart A. Adenosine-producing regulatory B cells in head and neck cancer. Cancer Immunol Immunother 2020.
• Wardak S. Human papillomavirus (HPV) and cervical cancer. Medycyna Doświadczalna i Mikrobiologia 2016; 68(1): 73–84.
• Chen Z, Zhu Y, Du R, Pang N, Zhang F, Dong D, Ding J, Ding Y. Role of Regulatory B Cells in the Progression of Cervical Cancer. Hindawi Mediators of Inflammation 2019; Article ID 6519427.
• Kim R, Emi M, Tanabe K. Cancer immunoediting from immune surveillance to immune escape. Immunology 2007; 121: 1–14.