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 o f B cells from a selected subpopulation of patients with CVID delineat ed by B cell surface marker analysis, in vitro ISE response, and molec ular markers of B cell V-H gene repertoire. These patients had altered display of B cell surface molecules that play a role in apoptosis. Th e patients' B cells had a 4.5-250-fold increase in CD95 (Apo-1, fas) e xpression and increased CD95 display on their T cells. CD38, a molecul e important in preventing germinal centre B cell apoptosis, was reduce d on the patients' B cells. The expression of this molecule was induci ble on the CVID lymphocytes with retinoic acid. Increased spontaneous apoptosis in vitro was observed with the patients' B (23%) and T cells (10%) compared with normal cells (13% and 3%, respectively). Stimulat ion in vitro with IL-4 and CD40 rescued the B cells from apoptosis and allowed for their differentiation. However, IL-4 plus alpha CD40-driv en immunoglobulin production was not quantitatively or qualitatively n ormal. Failure to overcome apoptosis, a normal step in germinal centre B cell development, may be involved in the lack of differentiation se en in this subset of CVID patients.