Plasma cell differentiation requires the transcription factor XBP-1

Considerable progress has been made in identifying the transcription factor s involved in the early specification of the B-lymphocyte lineage. However, little is known about factors that control the transition of mature activa ted B cells to antibody-secreting plasma cells. Here we report that the tra nscription factor XBP-1 is required for the generation of plasma cells. XBP -1 transcripts were rapidly upregulated in vitro by stimuli that induce pla sma-cell differentiation, and were found at high levels in plasma cells fro m rheumatoid synovium. When introduced into B-lineage cells, XBP-1 initiate d plasma-cell differentiation. Mouse lymphoid chimaeras deficient in XBP-1 possessed normal numbers of activated B lymphocytes that proliferated, secr eted cytokines and formed normal germinal centres. However, they secreted v ery little immunoglobulin of any isotype and failed to control infection wi th the B-cell-dependent polyoma virus, because plasma cells were markedly a bsent. XBP-1 is the only transcription factor known to be selectively and s pecifically required for the terminal differentiation of B lymphocytes to p lasma cells.