Regulation of Er homeostasis in b lymphocytes during common variable immunodeficiency

• Grant number: 09/51326-8
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2009
• End date: July 31, 2011
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Maristela Martins de Camargo
• Grantee: Maristela Martins de Camargo
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

During terminal differentiation of B lymphocytes into plasma cells the increase in translation of nascent immunoglobulins (Ig) leads to stress and expansion of the endoplasmic reticulum (ER), triggering a signaling pathway named Unfolded Protein Response (UPR). This pathway rescues ER homeostasis by matching its protein processing capabilities with its physiological demands. XBP-1 is the main transcription factor involved in UPR target gene transcription. XBP-1 mRNA must be spliced by endonuclease IRE-la to become active. Our previous studies identified one Common Variable Immunodeficiency (CVID) patient with defective splicing of XBP-1 mRNA. Co-localization of unfolded IgM chains and the ER were found in this patient, suggesting a defect on the folding but not synthesis of Igs. We also showed that this patient presents a slower kinetics of UPR activation when compared to a healthy individual. Current proposal aims at continuing this study, systematically analyzing the activation and deactivation kinetics of the UPR pathway in this patient. We will evaluate how exogenous chemical chaperones or over-expression of the chaperone BiP interfere with the phenotype of the cells of this patient. Finally, we aim to correlate the maturity and responsivity of the UPR pathway with the differentiation state of a B cell. Besides our previously identified patient, we will expand our molecular studies to new CVID patients. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

OLIVEIRA, CAMILA D.; LARSSON, CARLOS E.; DE CAMARGO, MARISTELA M.. Longitudinal assessment of T-lymphocyte subpopulations during generalized demodicosis in dogs and their relationship with remission. VETERINARY DERMATOLOGY, v. 26, n. 1, p. 18+, FEB 2015. (09/51326-8, 11/51778-6)

COSTA, C. Z. F.; DA ROSA, S. E. A.; DE CAMARGO, M. M.. The Unfolded Protein Response: How Protein Folding Became a Restrictive Aspect for Innate Immunity and B Lymphocytes. Scandinavian Journal of Immunology, v. 73, n. 5, p. 436-448, MAY 2011. (09/06529-8, 09/51326-8)