B cell lines from a subset of patients with common variable immunodeficiency undergo enhanced apoptosis associated with an increased display of CD95 (Apo-1/fas), diminished CD38 expression, and decreased IgG and IgA production

Abstract

Investigation of common variable immunodeficiency (CVI) is hampered by lack of a suitable in vitro models. We have developed EBV-transformed B lymphoblastoid cell lines from a selected subset of CVI patients and characterized them for phenotypic and functional properties that provide evidence for their representation of the CVI disease state. B cell lines from the patients expressed increased levels of sIgM and reduced levels of sIgD and sIgG. Essentially none of the CVI-derived B cell lines produced IgG and IgA while all produced IgM, in contrast to normal B cell lines that produced large amounts of IgG and IgM and detectable levels of IgA. Expression of CD95 (fas/Apo-1), a molecule that can induce apoptosis, was increased on the CVI B cell lines while CD38, a novel signaling molecule whose stimulation may prevent apoptosis, showed reduced expression. The B cell lines from the CVI patients exhibit increased apoptosis in vitro spontaneously, in response to anti-CD95 mAb and to X-irradiation. These phenotypic and functional changes are similar to findings on freshly derived B cells from the patients. EBV-derived B cell lines from patients with hyper-IgM immunodeficiency and X-linked agammaglobulinemia did not demonstrate increased CD95 expression or enhanced apoptosis. Thus the EBV-derived B cell lines from our selected CVI patients manifest many characteristics of the patients' fresh cells and may provide critical reagents for the further elucidation of the nature of the B cell dysfunction in the selected subset of CVI patients.