Plasma cell differentiation requires the transcription factor XBP-1

• Published in: Nature (London) Vol. 412; no. 6844; pp. 300 - 307
• Main Authors: Glimcher, Laurie H, Reimold, Andreas M, Iwakoshi, Neal N, Manis, John, Vallabhajosyula, Prashanth, Szomolanyi-Tsuda, Eva, Gravallese, Ellen M, Friend, Daniel, Grusby, Michael J, Alt, Frederick
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 19-07-2001; Nature Publishing Group
• Subjects: Animals; Antibody Formation; Antigens - immunology; Arthritis, Rheumatoid - immunology; B-Lymphocytes - cytology; B-Lymphocytes - immunology; Biological and medical sciences; Cell Differentiation; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Cells; Chimera; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Female; Fundamental and applied biological sciences. Psychology; Immune system; Immunophenotyping; Inflammation - immunology; Lymphocyte Activation; Lymphocytes; Mice; Molecular and cellular biology; Plasma; Plasma Cells - chemistry; Plasma Cells - immunology; Polyomavirus; Polyomavirus - immunology; Proteins; Regulatory Factor X Transcription Factors; Transcription Factors - physiology; X-Box Binding Protein 1; XBP-1 protein; Virus; Vertebrata; Phenotype; Mammalia; Mouse; Rodentia; Polyomavirus; B-Lymphocyte; Papovaviridae; Mutation; Plasmocyte; Cell differentiation
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/35085509

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.