The fate of human CD77+ germinal center B lymphocytes after rescue from apoptosis.

Germinal center (GC) B lymphocytes, defined by various criteria, have been shown to spontaneously undergo apoptosis in vitro unless they receive a positive signal. This rescue signal seems to be a multi-component process which involves not only the B cell receptor but also other cell surface receptors such as the CD40 antigen. In previous studies, we have shown that expression of the CD77 antigen is restricted to GC B lymphocytes and that CD77+ cells readily enter programmed cell death when cultured in vitro. In order to better characterize the CD77+ B lymphocytes, we have investigated the fate of these cells after rescue from apoptosis. Survival of CD77+ cells was achieved either with a combination of anti-CD40 mAb and IL4 (the CD40 system developed by Banchereau et al., (1991) Science 251, 70-72) or EBV infection. After 4 days of culture, similar phenotypic and functional changes of the CD77+ lymphocytes were observed in both systems: CD77 antigen was down-regulated, CD23 antigen which was originally negative became strongly expressed and the expression of CD38 and CD20 remained constant. Furthermore, large quantities of soluble CD23 were produced by the surviving cells. These results indicate that CD77 antigen is expressed by GC B cells which are highly susceptible to enter apoptosis but which are not doomed to die.