Plasma cell differentiation requires the transcription factor XBP-1

Andreas M. Reimold, Neal N. Iwakoshi, John Manis, Prashanth Vallabhajosyula, Eva Szomolanyi-Tsuda, Ellen M. Gravallese, Daniel Friend, Michael J. Grusby, Frederick Alt, Laurie H. Glimcher

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Abstract

Considerable progress has been made in identifying the transcription factors involved in the early specification of the B-lymphocyte lineage. However, little is known about factors that control the transition of mature activated B cells to antibody-secreting plasma cells. Here we report that the transcription factor XBP-1 is required for the generation of plasma cells. XBP-1 transcripts were rapidly upregulated in vitro by stimuli that induce plasma-cell differentiation, and were found at high levels in plasma cells from rheumatoid synovium. When introduced into B-lineage cells, XBP-1 initiated plasma-cell differentiation. Mouse lymphoid chimaeras deficient in XBP-1 possessed normal numbers of activated B lymphocytes that proliferated, secreted cytokines and formed normal germinal centres. However, they secreted very little immunoglobulin of any isotype and failed to control infection with the B-cell-dependent polyoma virus, because plasma cells were markedly absent. XBP-1 is the only transcription factor known to be selectively and specifically required for the terminal differentiation of B lymphocytes to plasma cells.

Original languageEnglish (US)
Pages (from-to)300-307
Number of pages8
JournalNature
Volume412
Issue number6844
DOIs
StatePublished - Jul 19 2001

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Reimold, A. M., Iwakoshi, N. N., Manis, J., Vallabhajosyula, P., Szomolanyi-Tsuda, E., Gravallese, E. M., Friend, D., Grusby, M. J., Alt, F., & Glimcher, L. H. (2001). Plasma cell differentiation requires the transcription factor XBP-1. Nature, 412(6844), 300-307. https://doi.org/10.1038/35085509