125 ALTERED PROTEIN KINASE C IN A PATIENT WITH COMMON VARIABLE IMMUNODEFICIENCY: A novel type of defect leading to immunodeficiency?

摘要

The aim of our studies is to identify genes involved in the pathogenesis of common variable immunodeficiency (CVI). One of our CVI patients with severely depressed mitogen response and defective B cell differentiation in response to T cell dependent and T cell independent stimulators, shows in addition a reduced CD 25 (IL 2 receptor) expression after T cell stimulation with mitogen. CD 25 expression is lacking on T cells and an EBV-immortalized B cell line (BCL) in response to stimulation with phorbol ester PMA, an activator of protein kinase C (PKC). Binding studies with phorbol ester on patient's BCL show that PKC is expressed at slightly increased numbers and affinity. Inhibition studies of proliferative responses to T cell mitogens with protein kinase inhibitors (H7, H8, HA1004) indicate that PKC is altered in patient's T cells. Our hypothesis is that immunodeficiency in this patient is caused by an alteration in a subspecies of PKC affecting activation of lymphocytes.