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 and Laurie H. Glimcher ()
Additional contact information
Andreas M. Reimold: Harvard School of Public Health
Neal N. Iwakoshi: Harvard School of Public Health
John Manis: Howard Hughes Medical Institute, Children's Hospital
Prashanth Vallabhajosyula: Harvard School of Public Health
Eva Szomolanyi-Tsuda: University of Massachusetts Medical School
Ellen M. Gravallese: Beth Israel Deaconess Medical Center
Daniel Friend: Harvard Medical School
Michael J. Grusby: Harvard School of Public Health
Frederick Alt: Howard Hughes Medical Institute, Children's Hospital
Laurie H. Glimcher: Harvard School of Public Health

Nature, 2001, vol. 412, issue 6844, 300-307

Abstract: 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.

Date: 2001
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DOI: 10.1038/35085509

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