Regulatory B cells: general characterization and evidence of their role in tumor immunity
DOI:
https://doi.org/10.33448/rsd-v9i2.2142Keywords:
Breg cells; IL-10; Tumor immunity.Abstract
Regulatory B cells (Bregs) are cells that modulate the immune response through secretion of interleukins such as IL-10, IL-35 and TGF-β. Different subsets of Breg cells vary not only in their phenotype, but also in their action mechanism. Studies have identified the presence of Breg cells during the development of some types of tumors. The aim of this paper is to survey the literature on some of the Bregs cell’s phenotypes, their origin and their immune response modulation mechanisms, as well as their role in some types of tumors. Regarding methodology, the SciELO and PubMed databases and theirs descriptors “regulatory B cells”, associated with “IL-10” and “tumor immunity” were used in order to survey both original and review articles. We found 108 articles referring to the subject from which 74 articles were selected taking into consideration the objectives proposed for this review. We conclude that there are several phenotypes of Breg cells and that these cells act mostly through immunosuppression mechanisms, thus enabling the development and progression of some diseases, such as cancer. Understanding the mechanisms by which Breg cells influence the immune response profile in certain diseases is important for designing safe and effective immunotherapies targeted at these cells.
References
Akdis, M., Trautmann, A., Klunker, S., Daigle, I., Küçüksezer, U., Deglmann, W., Blaser K. (2003). T helper (Th) 2 predominance in atopic diseases is due to preferential apoptosis of circulating memory/effector Th1 cells. The FASEB Journal, 17(9), 1026-1035.
Alhabbab, R., Nova-Lamperti, E., Aravena, O., Burton, H., Lechler, R., Dorling, A., & Lombardi, G. (2019). Regulatory B cells: Development, phenotypes, functions, and role in transplantation. Immunological Reviews.
Allman, D., Lindsley, R., DeMuth, W., Rudd, K., Shinton, S., & Hardy, R. (2001). Resolution of Three Nonproliferative Immature Splenic B Cell Subsets Reveals Multiple Selection Points During Peripheral B Cell Maturation. The Journal Of Immunology, 167(12), 6834-6840.
Ammirante, M., Luo, J. L., Grivennikov, S., Nedospasov, S., & Karin, M. (2010). B-cell-derived lymphotoxin promotes castration-resistant prostate cancer. Nature,464 (7286), 302–305.
Arabpour, M., Rasolmali, R., Talei, A., Mehdipour, F., & Ghaderi, A. (2019). Granzyme B production by activated B cells derived from breast cancer-draining lymph nodes. Molecular Immunology, 114, 172-178.
Beaudin, A., & Forsberg, E. (2016). To B1a or not to B1a: do hematopoietic stem cells contribute to tissue-resident immune cells?. Blood, 128(24), 2765-2769.
Brodt, P., & Gordon, J. (1978). Anti-tumor immunity in B lymphocyte-deprived mice. I. Immunity to a chemically induced tumor. Journal of immunology, 121(1), 359–362.
Cai, X., Zhang, L., & Wei, W. (2019). Regulatory B cells in inflammatory diseases and tumor. International Immunopharmacology, 67, 281-286.
Candando, K.M., Lykken, J.M., Tedder, T.F. (2008). B10 cell regulation of health and disease. Seminars In Immnunology, 20, 26-42.
Carter, N., Rosser, E., & Mauri, C. (2012). Interleukin-10 produced by B cells is crucial for the suppression of Th17/Th1 responses, induction of T regulatory type 1 cells and reduction of collagen-induced arthritis. Arthritis Research & Therapy, 14(1), R32.
Chen, Z., Zhu, Y., Du, R., Pang, N., Zhang, F., Dong, D., Ding, Y. (2019). Role of Regulatory B Cells in the Progression of Cervical Cancer. Mediators Of Inflammation, 2019, 1-8.
Collison, L., Workman, C., Kuo, T., Boyd, K., Wang, Y., Sehy, D., Vignali, K. (2007). The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature, 450(7169), 566-569.
Cunningham-Rundles, C. (2011). Autoimmunity in primary immune deficiency: taking lessons from our patients. Clinical & Experimental Immunology, 164, 6-11.
de Visser, K., Korets, L., & Coussens, L. (2005). De novo carcinogenesis promoted by chronic inflammation is B lymphocyte dependent. Cancer Cell, 7(5), 411-423.
Ding, Q., Yeung, M., Camirand, G., Zeng, Q., Akiba, H., & Yagita, H., Rothstein DM. (2011). Regulatory B cells are identified by expression of TIM-1 and can be induced through TIM-1 ligation to promote tolerance in mice. Journal Of Clinical Investigation, 121(9), 3645-3656.
Fillatreau, S., Sweenie, C., McGeachy, M., Gray, D., & Anderton, S. (2002). B cells regulate autoimmunity by provision of IL-10. Nature Immunology, 3(10), 944-950.
Forte, G., Sorrentino, R., Montinaro, A., Luciano, A., Adcock, I., & Maiolino, P., Morello, S. (2012). Inhibition of CD73 Improves B Cell-Mediated Anti-Tumor Immunity in a Mouse Model of Melanoma. The Journal Of Immunology, 189(5), 2226-2233.
Gondek, D., Lu, L., Quezada, S., Sakaguchi, S., & Noelle, R. (2005). Cutting Edge: Contact-Mediated Suppression by CD4+CD25+ Regulatory Cells Involves a Granzyme B-Dependent, Perforin-Independent Mechanism. The Journal Of Immunology, 174(4), 1783-1786.
Gunderson, A., & Coussens, L. (2013). B cells and their mediators as targets for therapy in solid tumors. Experimental Cell Research, 319(11), 1644-1649.
Han, S., Feng, S., Ren, M., Ma, E., Wang, X., Xu, L., & Xu, M. (2014). Glioma cell-derived placental growth factor induces regulatory B cells. The International Journal Of Biochemistry & Cell Biology, 57, 63-68.
Harris, D., Haynes, L., Sayles, P., Duso, D., Eaton, S., Lepak, N., Lund, F. (2000). Reciprocal regulation of polarized cytokine production by effector B and T cells. Nature Immunology, 1(6), 475-482.
Heeren, A., Koster, B., Samuels, S., Ferns, D., Chondronasiou, D., Kenter, G., Jordanova, E. (2015). High and Interrelated Rates of PD-L1+CD14+ Antigen-Presenting Cells and Regulatory T Cells Mark the Microenvironment of Metastatic Lymph Nodes from Patients with Cervical Cancer. Cancer Immunology Research, 3(1), 48-58.
Hsu, L., Li, K., Chu, K., & Chiang, B. (2015). A B-1a cell subset induces Foxp3− T cells with regulatory activity through an IL-10-independent pathway. Cellular & Molecular Immunology, 12(3), 354-365.
Hwang, I., Boularan, C., Harrison, K., & Kehrl, J. (2018). Gαi Signaling Promotes Marginal Zone B Cell Development by Enabling Transitional B Cell ADAM10 Expression. Frontiers In Immunology, 9.
Inoue, S., Leitner, W., Golding, B., & Scott, D. (2006). Inhibitory Effects of B Cells on Antitumor Immunity. Cancer Research, 66(15), 7741-7747.
Iwata, Y., Matsushita, T., Horikawa, M., DiLillo, D., Yanaba, K., Venturi, G., ... Tedder, T. (2011). Characterization of a rare IL-10–competent B-cell subset in humans that parallels mouse regulatory B10 cells. Blood, 117(2), 530-541.
Jahrsdörfer, B., Vollmer, A., Blackwell, S., Maier, J., Sontheimer, K., Beyer, T., Weiner, G. (2010). Granzyme B produced by human plasmacytoid dendritic cells suppresses T-cell expansion. Blood, 115(6), 1156-1165.
Kammertoens, T., Qin, Z., Briesemeister, D., Bendelac, A., & Blankenstein, T. (2012). B-cells and IL-4 promote methylcholanthrene-induced carcinogenesis but there is no evidence for a role of T/NKT-cells and their effector molecules (Fas-ligand, TNF-α, perforin). International Journal Of Cancer, 131(7), 1499-1508.
Katz, S., Parker, D., & Turk, J. (1974). B-cell suppression of delayed hypersensitivity reactions. Nature, 251(5475), 550-551.
Kinoshita, T., Ishii, G., Hiraoka, N., Hirayama, S., Yamauchi, C., Aokage, K., Ochiai, A. (2013). Forkhead box P3 regulatory T cells coexisting with cancer associated fibroblasts are correlated with a poor outcome in lung adenocarcinoma. Cancer Science, 104(4), 409-415.
Kobayashi, T., Hamaguchi, Y., Hasegawa, M., Fujimoto, M., Takehara, K., & Matsushita, T. (2014). B Cells Promote Tumor Immunity against B16F10 Melanoma. The American Journal Of Pathology, 184(11), 3120-3129.
Lampropoulou, V., Hoehlig, K., Roch, T., Neves, P., Gómez, E., Sweenie, C., Fillatreau, S. (2008). TLR-Activated B Cells Suppress T Cell-Mediated Autoimmunity. The Journal Of Immunology, 180(7), 4763-4773.
LeBien, T., & Tedder, T. (2008). B lymphocytes: how they develop and function. Blood, 112(5), 1570-1580.
Lee-Chang, C., Bodogai, M., Martin-Montalvo, A., Wejksza, K., Sanghvi, M., Moaddel, R., Biragyn, A. (2013). Inhibition of Breast Cancer Metastasis by Resveratrol-Mediated Inactivation of Tumor-Evoked Regulatory B Cells. The Journal Of Immunology, 191(8), 4141-4151.
Lindner, S., Dahlke, K., Sontheimer, K., Hagn, M., Kaltenmeier, C., Barth, T., Jahrsdörfer, B. (2013). Interleukin 21-Induced Granzyme B-Expressing B Cells Infiltrate Tumors and Regulate T Cells. Cancer Research, 73(8), 2468-2479.
Lundy, S. (2009). Killer B lymphocytes: the evidence and the potential. Inflammation Research, 58(7), 345-357.
Maseda, D., Candando, K., Smith, S., Kalampokis, I., Weaver, C., Plevy, S., Tedder, T. (2013). Peritoneal Cavity Regulatory B Cells (B10 Cells) Modulate IFN-γ+CD4+ T Cell Numbers during Colitis Development in Mice. The Journal Of Immunology, 191(5), 2780-2795.
Matsumoto, M., Baba, A., Yokota, T., Nishikawa, H., Ohkawa, Y., Kayama, H., Baba, Y. (2014). Interleukin-10-Producing Plasmablasts Exert Regulatory Function in Autoimmune Inflammation. Immunity, 41(6), 1040-1051.
Matsushita, T., Yanaba, K., Bouaziz, J., Fujimoto, M., & Tedder, T. (2008). Regulatory B cells inhibit EAE initiation in mice while other B cells promote disease progression. Journal Of Clinical Investigation, 118, 3420.
Mauri, C., Menon, M. (2006). The expanding family of regulatory B cells. International Immunology, 27, 479-486.
Meiler, F., Zimmermann, M., Blaser, K., Akdis, C., & Akdis, M. (2006). T-cell subsets in the pathogenesis of human asthma. Current Allergy And Asthma Reports, 6(2), 91-96.
Minagawa, R., Okano, S., Tomita, Y., Kishihara, K., Yamada, H., Nomoto, K., Nomoto, K. (2004). The Critical Role of Fas-Fas Ligand Interaction in Donor-Specific Transfusion-Induced Tolerance to H-Y Antigen. Transplantation, 78(6), 799-806.
Moach, P., Schreiber, H., & Rowley, D. (1993). CD4+ and B lymphocytes in transplantation immunity. II. Augmented rejection of tumor allografts by mice lacking B cells.Transplantation, 55(6), 1356-1360.
Nelson, B. (2010). CD20+ B Cells: The Other Tumor-Infiltrating Lymphocytes. The Journal Of Immunology, 185(9), 4977-4982.
Neta, R., & Salvin, S. B. (1974). Specific suppression of delayed hypersensitivity: the possible presence of a suppressor B cell in the regulation of delayed hypersensitivity. Journal of immunology,131(6), 1716–1725.
Nzula, S., Going, J. J., & Stott, D. I. (2003). Antigen-driven clonal proliferation, somatic hypermutation, and selection of B lymphocytes infiltrating human ductal breast carcinomas. Cancer research, 63(12), 3275–3280.
O'garra, A., Chang, R., Go, N., Hastings, R., Haughton, G., & Howard, M. (1992). Ly-1 B (B-1) cells are the main source of B cell-derived interleukin 10. European Journal Of Immunology, 22(3), 711-717.
Olkhanud, P., Damdinsuren, B., Bodogai, M., Gress, R., Sen, R., Wejksza, K., Biragyn, A. (2011). Tumor-Evoked Regulatory B Cells Promote Breast Cancer Metastasis by Converting Resting CD4+ T Cells to T-Regulatory Cells. Cancer Research, 71(10), 3505-3515.
Olkhanud, P., Rochman, Y., Bodogai, M., Malchinkhuu, E., Wejksza, K., Xu, M., Biragyn, A. (2011). Thymic Stromal Lymphopoietin Is a Key Mediator of Breast Cancer Progression. The Journal Of Immunology, 186(10), 5656-5662.
Pone, E. J., Zhang, J., Mai, T., White, C. A., Li, G., Sakakura, J. K., Patel, P. J., Al-Qahtani, A., Zan, H., Xu, Z., & Casali, P. (2012). BCR-signalling synergizes with TLR-signalling for induction of AID and immunoglobulin class-switching through the non-canonical NF-κB pathway. Nature Communications, 767.
Qian, L., Bian, G., Zhou, Y., Wang, Y., Hu, J., Liu, X., & Xu, Y. (2015). Short communication Clinical significance of regulatory B cells in the peripheral blood of patients with oesophageal cancer. Central European Journal Of Immunology, 2, 263-265.
Radbruch, A., Muehlinghaus, G., Luger, E., Inamine, A., Smith, K., Dörner, T., & Hiepe, F. (2006). Competence and competition: the challenge of becoming a long-lived plasma cell. Nature Reviews Immunology, 6(10), 741-750.
Rafei, M., Hsieh, J., Zehntner, S., Li, M., Forner, K., Birman, E., Galipeau, J. (2009). A granulocyte-macrophage colony–stimulating factor and interleukin-15 fusokine induces a regulatory B cell population with immune suppressive properties. Nature Medicine, 15(9), 1038-1045.
Rosser, E., & Mauri, C. (2015). Regulatory B Cells: Origin, Phenotype, and Function. Immunity, 42(4), 607-612.
Sarvaria, A., Madrigal, J., & Saudemont, A. (2017). B cell regulation in cancer and anti-tumor immunity. Cellular & Molecular Immunology, 14(8), 662-674.
Schioppa, T., Moore, R., Thompson, R., Rosser, E., Kulbe, H., Nedospasov, S., Balkwill, F. (2011). B regulatory cells and the tumor-promoting actions of TNF - during squamous carcinogenesis. Proceedings Of The National Academy Of Sciences, 108(26), 10662-10667.
Shah, S., Divekar, A., Hilchey, S., Cho, H., Newman, C., Shin, S., Rosenblatt, J. (2005). Increased rejection of primary tumors in mice lacking B cells: Inhibition of anti-tumor CTL and TH1 cytokine responses by B cells. International Journal Of Cancer, 117(4), 574-586.
Shen, P., Roch, T., Lampropoulou, V., O’Connor, R., Stervbo, U., Hilgenberg, E., Fillatreau, S. (2014). IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases. Nature, 507(7492), 366-370.
Song, S., Yuan, P., Li, P., Wu, H., Ni, W., Lu, J., & Wei, W. (2015). Protective Effects of Total Glucosides of Paeony on N-nitrosodiethylamine-induced Hepatocellular Carcinoma in Rats via Down-regulation of Regulatory B Cells. Immunological Investigations, 44(6), 521-535.
Tanwar, S., Dhar, A., Varanasi, V., Mukherjee, T., Boppana, R., Basak, S., Rath, S. (2017). Mediation of transitional B cell maturation in the absence of functional Bruton’s tyrosine kinase. Scientific Reports, 7(1).
Tedder, T. (2015). B10 Cells: A Functionally Defined Regulatory B Cell Subset. The Journal of Immunology, 194(4), 1395-1401.
Wang, R., Yu, C., Dambuza, I., Mahdi, R., Dolinska, M., Sergeev, Y., Egwuagu, C. (2014). Interleukin-35 induces regulatory B cells that suppress autoimmune disease. Nature Medicine, 20(6), 633-641.
Wang, Y., & Rothstein, T. (2012). Induction of Th17 cell differentiation by B-1 cells. Frontiers In Immunology, 3.
Wang, Y., Tsai, D., Ko, Y., Yang, T., Lin, I., Hung, K., & Lin, K. (2019). Blimp-1 Contributes to the Development and Function of Regulatory B Cells. Frontiers In Immunology, 10.
Wei, X., Jin, Y., Tian, Y., Zhang, H., Wu, J., Lu, W., & Lu, X. (2016). Regulatory B cells contribute to the impaired antitumor immunity in ovarian cancer patients. Tumor Biology, 37(5), 6581-6588.
Wejksza, K., Lee-Chang, C., Bodogai, M., Bonzo, J., Gonzalez, F., Lehrmann, E., … Biragyn, A. (2013). Cancer-Produced Metabolites of 5-Lipoxygenase Induce Tumor-Evoked Regulatory B Cells via Peroxisome Proliferator–Activated Receptor α. The Journal Of Immunology, 190(6), 2575-2584.
Yanaba, K., Bouaziz, J., Matsushita, T., Magro, C., St.Clair, E., & Tedder, T. (2008). B-lymphocyte contributions to human autoimmune disease. Immunological Reviews, 223(1), 284-299.
Yanaba, K., Bouaziz, J., Matsushita, T., Tsubata, T., & Tedder, T. (2009). The Development and Function of Regulatory B Cells Expressing IL-10 (B10 Cells) Requires Antigen Receptor Diversity and TLR Signals. The Journal Of Immunology, 182(12), 7459-7472.
Yang, M., Deng, J., Liu, Y., Ko, K., Wang, X., Jiao, Z., Lu, L. (2012). IL-10–Producing Regulatory B10 Cells Ameliorate Collagen-Induced Arthritis via Suppressing Th17 Cell Generation. The American Journal Of Pathology, 180(6), 2375-2385.
Yarchoan, M., Mohan, A., Dennison, L., Vithayathil, T., Ruggieri, A., Lesinski, G., Armstrong, T. (2019). MEK inhibition suppresses B regulatory cells and augments anti-tumor immunity. Plos One, 14(10), e0224600.
Zhang, Y., Eliav, Y., Shin, S., Schreiber, T., Podack, E., Tadmor, T., & Rosenblatt, J. (2013). B lymphocyte inhibition of anti-tumor response depends on expansion of Treg but is independent of B-cell IL-10 secretion. Cancer Immunology, Immunotherapy, 62(1), 87-99.
Zhang, Y., Gallastegui, N., & Rosenblatt, J. D. (2015). Regulatory B cells in anti-tumor immunity. International immunology, 27(10), 521–530.
Zhang, Y., Morgan, R., Podack, E., & Rosenblatt, J. (2013). B cell regulation of anti-tumor immune response. Immunologic Research, 57(1-3), 115-124.
Zhou, P., Qiu, J., LʼItalien, L., Gu, D., Hodges, D., Chao, C., & Schebye, X. (2010). Mature B Cells Are Critical to T-cell-mediated Tumor Immunity Induced by an Agonist Anti-GITR Monoclonal Antibody. Journal Of Immunotherapy, 33(8), 789-797.
Downloads
Published
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
