Identification of a subset of common variable immunodeficiency patients with impaired B-cell protein tyrosine phosphorylation

The mechanisms responsible for common variable immunodeficiency syndrome (C VID) are as yet unknown. In the present study, we show that the B-cell dysf unction in a subset of CVID patients is caused by defective protein tyrosin e phosphorylation (PTP). We demonstrated that the PTP level and immunoglobu lin (Ig) secretion malfunctions can be successfully repaired when normal pl asma membrane components are implanted into these patients' B cells. Stimul ation of CVID patients' peripheral blood mononucleated cells with anti-Ig a ntibody revealed that 7 of 11 patients had lower PTP levels than those foun d in the normal donor cells. Plasma membrane implantation to the cells of t hese patients resulted in elevated PTP levels which reached normal levels u pon stimulation with anti-human Ig antibody. The results revealed two disti nct groups of CVID patients. The first group included patients whose B cell s expressed low PTP levels after Ig stimulation. In these patients the plas ma membrane implantation restored the normal PTP level as well as the abili ty to secrete IgM and/or IgG after B-cell stimulation. In the second group, patients whose B cells expressed a normal PTP level after Ig stimulation, with no restoration of their ability to secrete Ig upon plasma membrane imp lantation and lipopolysaccharide stimulation. We conclude that the first gr oup has an early signal transduction defect located in the B-cell plasma me mbrane, while in the second group the defect is located elsewhere.