Defective expression of CD23 and autocrine growth-stimulation in Epstein-Barr virus (EBV)-transformed B cells from patients with Wiskott-Aldrich syndrome (WAS).

WAS is an X-linked, recessive, immune deficiency syndrome, characteristically associated with lymphocyte and platelet dysfunction. Peripheral B lymphocytes from WAS patients are nonresponsive to polysaccharide antigens and show reduced numbers of cells expressing the integral membrane glycoprotein, CD23. The release of CD23 proteolytic fragments, so-called soluble CD23 (sCD23), by B lymphoblasts and EBV-transformed B cell lines has previously been described, and these fragments have been shown to stimulate autocrine growth of these cells. We have found that the surface expression of CD23 is reduced on WAS compared with control EBV-B cells. Surface CD23 levels were reduced two-fold in four WAS cell lines (group I) and nine-fold in four other lines (group II). Group II WAS cell lines also showed reduced growth rates in serum-free medium when compared with group I cell lines and EBV-B cell lines from eight normal subjects. In contrast to the group II WAS lines, group I and EBV-B cells from normal individuals produced an autocrine-growth factor activity which could be absorbed by anti-CD23 antibodies. Immunoprecipitation of sCD23 from culture supernatants confirmed that group I WAS cell lines produced less sCD23, particularly the 37K fragment which was prevalent in control EBV-B cells. Northern analysis showed that CD23 mRNA levels were increased three-fold in group I and unchanged in group II WAS compared with normal EBV-B cell lines, suggesting that decreased surface expression in WAS EBV-B cells reflects post-transcriptional events. Together these results suggest that reduced cell surface expression and aberrant proteolysis of CD23 occurs in WAS patients' B lymphocytes and may contribute to impaired immune function in these patients.