IL-10-DRIVEN IMMUNOGLOBULIN PRODUCTION BY B-LYMPHOCYTES FROM IGA-DEFICIENT INDIVIDUALS CORRELATES TO INFECTION PRONENESS

In search for a possible explanation of the phenotypic heterogeneity i n IgA deficiency, we studied the function of B cells from IgA-deficien t (IgAd) individuals. Two groups of IgA individuals, one frequently in fected and one clinically apparently healthy, as well as normal contro ls, were studied. Peripheral blood mononuclear cells (PBMC) and B cell s from IgAd individuals and controls were cultured with Staphylococcus aureus Cowan I strain and with anti-CD40 MoAb presented on the CD32-t ransfected fibroblast cell line in the presence of IL-10. In this expe rimental system PBMC and B cells from the infection-prone IgAd individ uals produced only minute amounts of IgA. In contrast, PBMC and B cell s from healthy IgAd subjects secreted significantly more IgA1 and IgA2 in comparison with infection-prone IgAd patients (P<0.05). These data suggest that the abnormalities of B cell differentiation in IgAd coul d be of heterogeneous origin. Thus, whereas in healthy IgAd subjects I gA production may be efficiently up-regulated in vitro by addition of IL-10 to CD40-activated B cell culture, the corresponding B cell diffe rentiation does not occur in infection-prone IgAd patients. These obse rvations provide a conceptual framework for phenotypic heterogeneity i n IgAd subjects.