부산대학교 도서관

Summary: Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by hypogammaglobulinemia and different degrees of B cell compartment alteration. Memory B cell differentiation requires the orchestrated activation of several intracellular signaling pathways that lead to the activation of a number of factors, such as nuclear factor kappa B (NF‐κB) which, in turn, promote transcriptional programs required for long‐term survival. The aim of this study was to determine if disrupted B cell differentiation, survival and activation in B cells in CVID patients could be related to defects in intracellular signaling pathways. For this purpose, we selected intracellular readouts that reflected the strength of homeostatic signaling pathways in resting cells, as the protein expression levels of the Bcl‐2 family which transcription is promoted by NF‐κB. We found reduced Bcl‐2 protein levels in memory B cells from CVID patients. We further explored the possible alteration of this crucial prosurvival signaling pathway in CVID patients by analysing the expression levels of mRNAs from anti‐apoptotic proteins in naive B cells, mimicking T cell‐dependent activation in vitro with CD40L and interleukin (IL)‐21. BCL‐XL mRNA levels were decreased, together with reduced levels of AICDA, after naive B‐cell activation in CVID patients. The data suggested a molecular mechanism for this tendency towards apoptosis in B cells from CVID patients. Lower Bcl‐2 protein levels in memory B cells could compromise their long‐term survival, and a possible less activity of NF‐κB in naive B cells, may condition an inabilityto increase BCL‐XL mRNA levels, thus not promoting survival in the germinal centers. [ABSTRACT FROM AUTHOR]