Recombinant 25‐kDa CD23 and interleukin 1α promote the survival of germinal center B cells: evidence for bifurcation in the development of centrocytes rescued from apoptosis

Abstract

Germinal centers contain a proliferating pool of centroblasts which give rise to non-dividing centrocyte. Centrocytes are programmed to die by apoptosis unless they receive a positive signal for rescue. 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 findings provide a functional rationale to the high level expression of CD23 found within a discrete subset of FDC and indicate a bifurcation in the development of germinal center B cells following their rescue from apoptosis.

Autocrine proliferating B cells are susceptible to terminal differentiation and apoptosis

“…Addition of IL-10, however, did not prevent apoptosis of the cells in presence of ionomycin plus PBU 2 . This is in accordance to the report that in lymphoma cells IL-10 expression does not protect from calciummediated apoptosis (Levy and Brouet, 1994;Liu et al, 1991). In B-CLL cells, IL-10 exhibits proapoptotic activities (Fluckiger et al, 1994) whereas the apoptosis of germinal center B cells is prevented by IL-10 (Levy and Brouet, 1994).…”

Functional B-cell response in intrahepatic lymphoid follicles in chronic hepatitis C

“…31 CD23 was diffusely stained in the GCs of lymph nodes and was closely related to IgM ϩ cells in the GCs (Fig. 3, upper panel).…”

Analyses of the In Vivo Trafficking of Stoichiometric Doses of an Anti-Complement Receptor 1/2 Monoclonal Antibody Infused Intravenously in Mice

“…This CR1/2 may represent FDC-associated CR1/2 that is less labile and less susceptible to proteolysis than B cell CR1/2 (57,58). Whether the localized mAb 7G6 is held on FDC by Fc␥R (30,31), or in part by FDCassociated CR1/2, or by CD23, which binds CR2 in primates (59,60), is not revealed presently, but this question may be addressed in appropriate knockout animals. Support for proteolytic release of extracellular B cell CR1/2 is also found in studies that indicated cleavage of a structurally related protein, primate E CR1, is required for the transfer of CR1-bound IC from E to acceptor cells (61)(62)(63).…”