Plasma cell differentiation requires the transcription factor XBP-1
Department of Medicine, Division of Rheumatology; Department of Pathology
Animals; Antibody Formation; Antigens; Arthritis, Rheumatoid; B-Lymphocytes; *Cell Differentiation; Chimera; DNA-Binding Proteins; Female; Immunophenotyping; Inflammation; Lymphocyte Activation; Mice; Plasma Cells; Polyomavirus; Transcription Factors
Cellular and Molecular Physiology | Immunopathology
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.
DOI of Published Version
Nature. 2001 Jul 19;412(6844):300-7. Link to article on publisher's site
Reimold, Andreas M.; Iwakoshi, Neal N.; Manis, John; Vallabhajosyula, Prashanth; Szomolanyi-Tsuda, Eva; Gravallese, Ellen M.; Friend, Daniel; Grusby, Michael J.; Alt, Frederick; and Glimcher, Laurie H., "Plasma cell differentiation requires the transcription factor XBP-1" (2001). Rheumatology Publications and Presentations. 31.