Células B regulatórias: caracterización general y evidencia de su papel en la inmunidad tumoral
DOI:
https://doi.org/10.33448/rsd-v9i2.2142Palabras clave:
Células Breg; IL-10; Inmunidad tumoralResumen
Las células B regulatórias (Bregs) son células que modulan la respuesta inmune a través de la secreción de interleucinas como IL-10, IL-35 y TGF-β. Los diferentes subconjuntos de células Bregs varían no solo en su fenotipo, sino también en su mecanismo de acción. Algunos estudios han identificado la presencia de células Bregs durante el desarrollo de algunos tipos de tumores. El objetivo de este trabajo fue estudiar la literatura sobre algunos de los fenotipos de células Bregs, su origen, sus mecanismos de modulación de la respuesta inmune, así como su papel en algunos tipos de tumores. Como metodología, se utilizaron las bases de datos SciELO y PubMed y los descriptores “células B regulatórias”, asociadas con “IL-10” e “inmunidad tumoral” para examinar artículos originales y revisar. Se encontraron 108 artículos que hacen referencia al tema y se seleccionaron 74 artículos teniendo en cuenta los objetivos propuestos para esta revisión. Se concluye que hay varios fenotipos de células Bregs y que estas células actúan principalmente a través de mecanismos de inmunosupresión, favoreciendo así el desarrollo y la progresión de algunas enfermedades, como el cáncer. Comprender los mecanismos por los cuales las células de Bregs influyen en el perfil de respuesta inmune en determinadas enfermedades es importante para diseñar inmunoterapias seguras y efectivas dirigidas a estas células.
Citas
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.
Descargas
Publicado
Cómo citar
Número
Sección
Licencia
Los autores que publican en esta revista concuerdan con los siguientes términos:
1) Los autores mantienen los derechos de autor y conceden a la revista el derecho de primera publicación, con el trabajo simultáneamente licenciado bajo la Licencia Creative Commons Attribution que permite el compartir el trabajo con reconocimiento de la autoría y publicación inicial en esta revista.
2) Los autores tienen autorización para asumir contratos adicionales por separado, para distribución no exclusiva de la versión del trabajo publicada en esta revista (por ejemplo, publicar en repositorio institucional o como capítulo de libro), con reconocimiento de autoría y publicación inicial en esta revista.
3) Los autores tienen permiso y son estimulados a publicar y distribuir su trabajo en línea (por ejemplo, en repositorios institucionales o en su página personal) a cualquier punto antes o durante el proceso editorial, ya que esto puede generar cambios productivos, así como aumentar el impacto y la cita del trabajo publicado.
