T-independent antigens induce the formation of long-lived plasma cells (132.18)

Abstract

Abstract Long-lived plasma cells (PCs) are terminally differentiated B cells that reside in the spleen and bone marrow where they secrete antibody for a life-time. Although PCs are the cellular arbiters of humoral immunity, the signals required for formation of long-lived antibody secreting PCs remain poorly defined. In addition, how long-lived PCs resist apoptosis in response to ionizing radiation (IR) is also not understood. We find that resistance to IR-induced apoptosis occurs exceptionally early, within three days, during PC differentiation. IR-resistance is even established in PCs following immunization with NP-LPS, a type 1 thymus-independent (TI-1) antigen thought to generate only short-lived PCs. We have exploited this finding by administering IR in vivo to investigate the lifespan of antigen-specific NP-LPS induced PCs months after immunization. Contrary to current models, we find immunization with NP-LPS, a response which neither requires T-cell help nor elicits germinal center formation, is sufficient to drive the formation of long-lived IR-resistant PCs. Further, we find that resistance to IR-induced apoptosis is a cell intrinsic property unique to PCs and is not shared by other activated B cells. These findings establish radioresistance as a novel property of very early PCs and challenge the popular view that TI-1 antigens are unable to elicit the formation of long-lived PCs.