B cell lines as models for inherited phagocytic diseases: abnormal superoxide generation in chronic granulomatous disease and giant granules in Chediak-Higashi syndrome.

Abstract

Epstein Barr virus (EBV)-transformed B cell lines (BCL) were developed from peripheral blood lymphocytes of individuals with Chediak-Higashi syndrome (CHS) and chronic granulomatous disease (CGD), and were compared to EBV BCL from normals. The cells that were studied expressed both B cell surface antigens and EBV nuclear antigens. BCL from normals contained small cytoplasmic granules. When stimulated with phorbol myristate acetate (PMA), these B cells reduced nitroblue tetrazolium (NBT) and generated significant amounts of superoxide. However, two other phagocytic stimuli, A23187 and f-methionine-leucine-phenylalanine, failed to stimulate BCL oxygen metabolism. BCL from seven individuals with CGD failed to either reduce NBT or generate superoxide on PMA stimulation, although the lines were morphologically similar to BCL from normals. In contrast, CHS-BCL generated superoxide more rapidly than did normals, and contained the characteristic giant granules of CHS. Thus, continuous BCL evidencing the phenotypic abnormalities of inherited human phagocytic diseases can provide large numbers of cells for biochemical and genetic study.