Defective Bcl‐2 expression in memory B cells from common variable immunodeficiency patients

In this study we provide for the first time an analysis of Bcl‐2 levels in various B‐cell subpopulations and antiapoptotic mRNA expression assays after CD40L and IL‐21 stimulation in naïve B cells of CVID patients. B cells from healthy donors presented an increase in Bcl‐2 intracellular expression in the transition from naïve to switched memory B cells. In contrast, this increase was reduced in CVID patients. We found reduced Bcl‐2 protein levels in memory B cells from CVID patients. We further explored the possible alteration of this crucial pro‐survival signalling pathway in CVID patients, by analysing the expression levels of mRNAs from antiapoptotic proteins in naïve B cells, mimicking T‐cell dependent activation in vitro with CD40L and IL‐21. BCL‐XL mRNA levels were decreased, together with reduced levels of AICDA, after naïve B‐cell activation in CVID patients. Our data suggested a molecular mechanism for a tendency toward apoptosis in B cells from CVID patients in relation to NFkB driven transcription. Lower Bcl‐2 protein levels in memory B cells could compromise their long‐term survival, and a possible less activity of NFkB in naïve B cells, munable to increase BCL‐XL mRNA levels, thus not promoting survival in the germinal centers.