Suppression of apoptosis in normal and neoplastic human B lymphocytes by CD40 ligand is independent of Bcl‐2 induction

Abstract

The tendency of isolated germinal center (GC) B cells to undergo apoptosis was suppressed by recombinant cell‐bound CD40 ligand (CD40L): after 2 days at 37°C, > 80 % of cells remained viable in the presence of CD40L as compared to < 1 % in control cultures. CD40L sustained a high rate of DNA synthesis in GC cells and was more effective than monoclonal antibody to CD40 in this regard. Group I Burkitt lymphoma (BL) cell lines induced to undergo apoptosis with anti‐immunoglobulin or calcium ionophore were also protected by CD40L. In BL cells, this route of rescue was not accompanied by induction of Bcl‐2 protein, the expression of which has been linked to hemopoietic cell survival. Bcl‐2 was induced in GC cells responding to CD40L, but its appearance was a relatively late event not reaching significant levels over controls until day 2 of culture. Thus induction of Bcl‐2 appears to be secondary to the survival signal imparted by CD40L. These findings are discussed in relation to a potential role for CD40L in supporting B cell tumors in vivo and the discovery that the molecular defect in the X‐linked Hyper‐IgM syndrome is targeted to the CD40L gene.