B cells from a distinct subset of patients with common variable immunodeficiency (CVID) have increased CD95 (Apo‐1/fas), diminished CD38 expression, and undergo enhanced apoptosis
We investigated the role of apoptosis in the differentiation failure of B cells from a selected subpopulation of patients with CVID delineated by B cell surface marker analysis, in vitro. IgE response, and molecular markers of B cell VH gene repertoire. These patients had altered display of B cell surface molecules that play a role in apoptosis. The patients' ‘B cells had a 4.5 250‐fold increase in CD95 (Apo‐I. fas) expression and increased CD95 display on their T cells. CD38. a molecule important in preventing germinal centre B cell apoptosis. was reduced on the patients’ B cells. The expression of this molecule was inducible on the CVID lymphocytes with retinoic acid. Increased spontaneous apoptosis in vitro. was observed with the patients’B (23%) and T ceils (10%) compared with normal cells (13% and 3%, respectively). Stimulation in vitro. with IL‐4 and CD40 rescued the B cells from apoptosis and allowed for their differentiation. However, IL‐4 plus aCD40‐driven immunoglobulin production was not quantitatively or qualitatively normal. Failure to overcome apoptosis, a normal step in germinal centre B cell development, may be involved in the lack of differentiation seen in this subset of CVID patients.