Radiation resistance is a property of long-lived plasma cells but not their precursors

Abstract Introduction Irradiation and reconstitution has often been used to analyse plasma cell turnover. Here, we characterised the kinetics of plasma cell reconstitution following irradiation, focussing on representation of recipient and donor plasma cells. Methods In a first setup, bone marrow chimeras were generated using congenic Ly5 allotype marked bone marrow transfer after lethal X-ray irradiation. Representation of donor and recipient B cells and plasma cells were tracked in the weeks thereafter. In a second setup, we repeated the reconstitution using plasma cell timestamp mice as recipients and BLIMP1gfp as donor bone marrow, allowing tracing of both recipient- and donor-source plasma cells with fluorescent reporters. Results In recipient spleen and bone marrow in the first setup, B cell and plasma cell numbers returned to homeostasis within 4 weeks of reconstitution. We determined that while B cells were essentially donor-derived by 4 weeks and plasma cells reached maximum donor representation at 4 weeks, they retained a significant fraction of recipient origin plasma cells to at least 8 weeks, the experiment endpoint. This clearly resolved plasma cell origin and revealed recipient plasma cells comprised both persistent and newly formed, the latter being the majority. When irradiated, timestamped mice were reconstituted with B-cell-insufficient µMT bone marrow, leaving irradiated recipient B cells as the sole source of new plasma cells, the recipients generated significantly more nascent plasma cells from endogenous B cells than occurred in the BLIMP1gfp recipients. Conclusion These data suggest that irradiated B cells are at a disadvantage to donor-derived B cells but can give rise to plasma cells when competition is alleviated, here by donor B cell lymphopenia. Bone marrow reconstitution after irradiation thus reveals a population of radiation resistant long-lived plasma cells and B cell or early-stage plasma cell competition for production and retention.