RECOMBINANT 25-KDA CD23 AND INTERLEUKIN-1-ALPHA PROMOTE THE SURVIVAL OF GERMINAL CENTER B-CELLS - EVIDENCE FOR BIFURCATION IN THE DEVELOPMENT OF CENTROCYTES RESCUED FROM APOPTOSIS

Germinal centers contain a proliferating pool of centroblasts which give rise to non-dividing centrocytes. Centrocytes are programmed to die by apoptosis unless they receive a positive signal for rescule. Rescue, in vivo, is likely to be dependent, initially, on interaction with antigen held on follicular dendritic cells (FDC). A subset of FDC located in that part of the germinal center furthest from centroblasts is particularly rich in CD23. Supernatants containing high levels of soluble CD23 were found not only to encourage the survival of germinal center B cells but also to promote their differentiation toward a plasmacytoid morphology; these activities were diminished following removal of CD23 from the supernatants. Recombinant 25-kDa CD23 was initially found to be incapable of providing the signal for germinal center cell development but on the addition of interleukin 1-alpha which, by itself, was inactive, rescue and differentiation of germinal center B cells were now achieved. Apoptosis in germinal center cells could also be prevented by the ligation of surface CD40 with monoclonal antibody: however, rescue via this pathway was not accompanied by plasmacytoid differentiation. These finding provide a functional rationale to the high level expression of CD23 found within a discrete subset of FDC and indicate a bifuraction in the development of germinal center B cells following their rescue from apoptosis.