Plasma cell differentiation requires the transcription factor XBP-1

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 tra...

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Bibliographic Details
Published in:Nature (London) 2001-07, Vol.412 (6844), p.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: Article
Language:English
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
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
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Summary: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.
ISSN:0028-0836
1476-4687
DOI:10.1038/35085509