B lymphocyte‐induced maturation protein‐1 (Blimp‐1) is sufficient to trigger an unfolded protein response and XBP‐1 processing in B cells

Terminal differentiation of B cells into antibody secreting plasma cells is an essential step for eliciting a successful humoral immune response. The two transcription factors B lymphocyte-induced maturation protein-1 (Blimp-1) and X-box-binding protein-1 (XBP-1) are indispensable for this process. Hereby, XBP-1 activation depends on Blimp-1. However, it is not known if Blimp-1 alone, in the absence of differentiation signals, can induce XBP-1 processing. Here we show that ectopic expression of Blimp-1 is sufficient to induce an unfolded protein response (UPR), as evidenced by the generation of the processed form of XBP-1 and upregulation of the classical UPR target BIP, in both the B cell lymphoma cell line WEHI 231 and in mouse primary splenic B cells. Interestingly, the amino terminal part of Blimp-1 comprising amino acids 1-751 was sufficient to induce the above effects while the carboxy terminal part comprising amino acids 465-856 had no effect. Taken together our results identify Blimp-1 as the upstream molecule, capable of triggering the UPR in B cells resulting in XBP-1 processing, which is an important step during plasma cell generation.