Differential expression of LRBA protein in human naive and memory B lymphocytes
DOI:
https://doi.org/10.17533/udea.acbi.v42n112a05Keywords:
apoptosis, flow cytometry, primary immunodeficiency diseases, naïve B cells, memory B cells, proliferation assaysAbstract
LRBA deficiency (Lipopolysaccharide-responsive and beige-like anchor protein) is a primary immunodeficiency caused by a defective expression of the intracellular protein LRBA, due to homozygous and heterozygous composed mutations in the corresponding gene. Patients with this immunodeficiency have a wide spectrum of clinical manifestations that include mainly immunodeficiency and autoimmunity. LRBA deficiency is associated with a decrease in class-switched memory B cells in peripheral blood and plasmablasts count, and a specific antibody response defective, as well as a defect in apoptosis and autophagy. In this study, intracellular differential expression of the LRBA protein in naïve and memory B cells of human peripheral blood was evaluated under different conditions by flow cytometry. We evidence that memory B cells have a higher expression of LRBA; on the other hand, we demonstrate that the expression of this protein in the B cells increases considerably under activation conditions; however, the magnitude of the increase in LRBA expression under this condition is higher in naïve B cells. In contrast, we show that the expression of this protein decreases in B cells undergoing to apoptosis, although even under these conditions, it is higher in memory B cells. These findings suggest that LRBA plays an important role in the development of humoral immune memory.
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Alkhair, O., Abolhassani, H., Rezaei, N., Fang, M., Kasper, V., Chavoshzadeh, Z., Mohammadzadeh, I., Mariam, A., Massaad, M., Chou, J., Aghamohammadi, A., y Geha, R. (2016). Spectrum of Phenotypes Associated with Mutations in LRBA. Journal Clinical Immunology, 36, 33. DOI: 10.1007/s10875-015-0224-7
Antonsson, A., y Persson, J.L. (2009). Induction of Apoptosis by Staurosporine Involves the Inhibition of Expression of the Major Cell Cycle Proteins at the G2/M Checkpoint Accompanied by Alterations in Erk and Akt Kinase Activities. Anticancer Research, 29, 2893-2898. http://ar.iiarjournals.org/content/29/8/2893.full
Antunes, R.F., Kaski, J.C., y Dumitriu, I.E. (2012). The Role of Costimulatory Receptors of the Tumour Necrosis Factor Receptor Family in Atherosclerosis. Journal of Biomedicine and Biotechnology, 464532. DOI: 10.1155/2012/464532
Brenner, D., Golks, A., Becker, M., Müller, W., Frey, C.R., Novak, R., Melamed, D., Kiefer, F., Krammer, P.H., y Arnold, R. (2007). Caspase-cleaved HPK1 induces CD95L-independent activation-induced cell death in T and B lymphocytes. Blood, 110, 3968-3977. DOI: 10.1182/blood-2007-01-071167
Cullinane, A.R., Schäffer, A.A., y Huizing, M. (2013). The BEACH is hot: a LYST of emerging roles for BEACH-domain containing proteins in human disease. Traffic, 14, 749-66. DOI: 10.1111/tra.12069
Erazo-Borras, L.V., Alvarez-Alvarez, J.A., Perez-Romero, C.A., Orrego-Arango, J.C., Franco-Restrepo, J.L., y Trujillo-Vargas, C.M. (2017). Skewed Invariant Natural Killer T (iNKT) Cells, Impaired iNKT:B Cell Help and Decreased SAP Expression in Blood Lymphocytes from Patients with Common Variable Immunodeficiency. Scandinavian Journal of Immunology, 86(3), 171-178. DOI: 10.1111/sji.12576
Espinosa, F.J., Condino, A., Franco, J.L., y Sorensen, R.U. (2016). En acción: para mejorar el acceso a la atención óptima para todos los pacientes con inmunodeficiencias primarias. Revista Alergia México, 63, 109-112. DOI: 10.18233/APM37No2pp64-68
Fecteau, J.F., Roy, A., y Néron, S. (2009). Peripheral blood CD27+ IgG+ B cells rapidly proliferate and differentiate into immunoglobulin-secreting cells after exposure to low CD154 interaction. Immunology, 128(1 Pt 2), e353-e365. DOI: 10.1111/j.1365-2567.2008.02976.x
Gámez-Díaz, L., August, D., Stepensky, P., Revel-Vilk, S., Seidel, M.G., Noriko, M., Morio, T., Worth, A.J.J., Blessing, J., Van de Veerdonk, F., Feuchtinger, T., Kanariou, M., Schmitt-Graeff, A., Jung, S., Seneviratne, S., Burns, S., Belohradsky, B.H., Rezaei, N., Bakhtiar, S., Speckmann, C., Jordan, M., y Grimbacher, B. (2016). The extended phenotype of LPS-responsive beige-like anchor protein (LRBA) deficiency. The Journal of Allergy and Clinical Inmunology, 137, 223-230. DOI: 10.1016/j.jaci.2015.09.025
Gámez-Díaz, L., Sigmund, E.C., Reiser, V., Vach, W., Jung, S., y Grimbacher, B. (2018). Rapid Flow Cytometry-Based Test for the Diagnosis of Lipopolysaccharide Responsive Beige-Like Anchor (LRBA) Deficiency. Frontiers in Immunology, 9, 720. DOI: 10.3389/fimmu.2018.00720
Good, K.L., Bryant, V.L., y Tangye, S.G. (2006). Kinetics of Human B Cell Behavior and Amplification of Proliferative Responses following Stimulation with IL-21. Journal of Immunology, 177, 5236-5247. DOI: 10.4049/jimmunol.177.8.5236
Klein, U., Rajewsky, K., y Küppers, R. (1998). Human immunoglobulin (Ig)M+IgD+ peripheral blood B cells expressing the CD27 cell surface antigen carry somatically mutated variable region genes: CD27 as a general marker for somatically mutated (memory) B cells. The Journal of Experimental Medicine, 188, 1679–1689. DOI: 10.1084/jem.188.9.1679
Korniluk, A., Kemona, H., y Dymicka-Piekarska, V. (2014). Multifunctional CD40L: pro- and anti-neoplastic activity. Tumor Biology, 35, 9447–9457. DOI: 10.1007/s13277-014-2407-x
Lo, B., Zhang, K., Lu, W., Zheng, L., Zhang, Q., Kanellopoulou, C., Zhang, Y., Liu, Z., Fritz, J.M., Marsh, R., Husami, A., Kissell, D., Nortman, S., Chaturvedi, V., Haines, H., Young, L.R., Mo, J., Filipovich, A.H., Bleesing, J.J., Mustillo, P., Stephens, M., Rueda, C.M., Chougnet, C.A., Hoebe, K., McElwee, J., Hughes, J.D., Karakoc-Aydiner, E., Matthews, H.F., Price, S., Su, H.C., Koneti Rao, V., Lenardo, M.J., y Jordan, M.B. (2015). Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy. Science, 349, 436-440. DOI: 10.1126/science.aaa1663
Lopez-Herrera, G., Tampella, G., Pan-Hammarström, Q., Herholz, P., Trujillo-Vargas, C.M., Phadwal, K., Simon, A.K., Moutschen, M., Etzioni, A., Mory, A., Srugo, I., Melamed, D., Hultenby, K., Liu, C., Baronio, M., Vitali, M., Philippet, P., Dideberg, V., Aghamohammadi, A., Rezaei, N., Enright, V., Du, L., Salzer, U., Eibel, H., Pfeifer, D., Veelken, H., Stauss, H., Lougaris, V., Plebani, A., Gertz, E.M., Schäffer, A.A., Hammarström, L., y Grimbacher, B. (2012). Deleterious Mutations in LRBA Are Associated with a Syndrome of Immune Deficiency and Autoimmunity. (2012). American Journal of Human Genetics, 90, 986-1001. DOI: 10.1016/j.ajhg.2012.04.015.
Marasco, E., Farroni, C., Cascioli, S., Marcellini, V., Scarsella, M., Giorda, E., Piano Mortari, E., Leonardi, L., Scarselli, A., Valentini, D., Cancrini, C., Duse, M., Grimsholm, O., y Carsetti, R. (2017). B-cell activation with CD40L or CpG measures the function of B-cell subsets and identifies specific defects in immunodeficient patient. European Journal of Immunology, 47, 131–143. DOI: 10.1002/eji.201646574
Morbach H., Eichhorn, E.M., Liese, J.G., y Girschick, H.J. (2010). Reference values for B cell subpopulations from infancy to adulthood. Clinical and Experimental Immunology, 162, 271–279. DOI:10.1111/j.1365-2249.2010. 04206.x
Pozo-Beltrán, C.F., Suárez-Gutiérrez, M.A., Yamazaki-Nakashimada, M.A., Medina-Vera, I., Saracho-Weber. F., Macías-Robles, A.P., Guzmán-Martínez, M.N., Navarrete-Rodríguez, E.M., Del Rio-Navarro, B.E., Espinosa-Padilla, S.E., y Blancas-Galicia, L. (2019). B subset cells in patients with chronic granulomatous disease in a Mexican population. Allergologia et Immunopathologia, 47, 372-377. DOI: 10.1016/j.aller.2019.03.005
Revel-Vilk, S., Fischer, U., Keller, B., Nabhani, S., Gámez-Díaz, L., Rensing-Ehl, A., Gombert, M., Hönscheid, A., Saleh, H., Shaag, A., Borkhardt, A., Grimbacher, B., Warnatz, K., Elpeleg, O., y Stepensky, P. (2015). Autoimmune lymphoproliferative syndrome-like disease in patients with LRBA mutation. Clinical Immunology, 159, 84-92. DOI: 10.1016/j.clim.2015.04.007
Sigismund, S., Argenzio, E., Tosoni, D., Cavallaro, E., Polo S., y Di Fiore, P.P. (2008). Clathrin-Mediated Internalization Is Essential for Sustained EGFR Signaling but Dispensable for Degradation. Developmental Cell, 15, 209-19. DOI: 10.1016/j.devcel.2008.06.012
Sorkin, A., y Goh, L.K. 2008. Endocytosis and intracellular trafficking of ErbBs. Experimental Cell Research, 314, 3093–3106. DOI: 10.1016/j.yexcr.2008.07.029
Tangye, S.G., y Good, K.L. (2007). Human IgM+CD27+ B Cells: Memory B Cells or “Memory” B Cells? Journal of Immunology, 179, 13-19. DOI: 10.4049/jimmunol.179.1.13
Vélez, A.C., Castaño, D.M., Gómez, R.D., Orrego, J.C., Moncada, M., y Franco, J.L. (2015). Inmunodeficiencia común variable: caracterización clínica e inmunológica de pacientes e identificación de subgrupos homogéneos con base en la tipificación de subpoblaciones de linfocitos B. Biomédica, 35, 101-16. DOI: 10.7705/biomedica.v35i1.2401
Wang, J.W., Howson, J., Haller, E., y Kerr, W.G. (2001). Identification of a Novel Lipopolysaccharide-Inducible Gene with Key Features of Both a Kinase Anchor Proteins and chs1/beige Proteins. Journal of Immunology, 166, 4586-4595. DOI: 10.4049/jimmunol.166.7.4586
Wang, J-W., Gamsby, J.J., Highfill, S.L., Mora, L.B., Bloom, G.C, Yeatman, T.J, Pan, T., Ramne, A.L., Chodosh, L.A., Douglas Cress, W., Chen, J., y Kerr W.G. (2004). Deregulated expression of LRBA facilitates cancer cell growth. Oncogene, 23, 4089–4097. DOI: 10.1038/sj.onc.1207567
Wang, J-W., y Lockey, R.F. (2014). Lipopolysaccharide-responsive beige-like anchor (LRBA), a novel regulator of human immune disorders. Austin Journal of Clinical Immunology, 1, 1004. https://austinpublishinggroup.com/clinical-immunology/fulltext/ajci-v1-id1004.php
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