Epstein-Barr virus-induced immunoglobulin synthesis by B cells from individuals with late-onset panhypogammaglobulinemia

Abstract

Epstein-Barr virus (EBV) transformation was used to examine the differentiation potential of circulating B cells from eight individuals with late-onset panhypogammaglobulinemia. Cytoplasmic and secreted immunoglobulins were evaluated by immunofluorescence and radioimmunoassay. EBV-infected cultures of B cells from patients and healthy controls generated similar numbers of IgM-secreting plasma cells, but relatively few IgG and IgA plasma cells were induced in cultures of patients' B cells. As further evidence of B-cell immaturity, approximately 90% of the IgA B cells in the eight patients coexpressed IgM. Clonal diversity of B cells from hypogammaglobulinemic patients was examined with a panel of mouse monoclonal antibodies directed against idiotypic and VH subgroup determinants. The frequencies of EBV-induced plasma cells exhibiting the different idiotypic and VH determinants were similar for patients and controls. The data suggest the continued generation of clonally diverse B cells that are capable of terminal plasma-cell differentiation when the normal triggering mechanisms are bypassed by EBV. The arrested differentiation at an immature B-cell stage in these hypogammaglobulinemic individuals would appear to reflect a defect in normal B-cell triggering.