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 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.
Reimold
A M
AM
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Iwakoshi
N N
NN
Manis
J
J
Vallabhajosyula
P
P
Szomolanyi-Tsuda
E
E
Gravallese
E M
EM
Friend
D
D
Grusby
M J
MJ
Alt
F
F
Glimcher
L H
LH
D000818:Animals; D000917:Antibody Formation; D000941:Antigens / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation; D002678:Chimera; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D016130:Immunophenotyping; D007249:Inflammation / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D010950:Plasma Cells / Q000737:chemistry* / Q000276:immunology; D011120:Polyomavirus / Q000276:immunology; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000502:physiology*; D000071717:X-Box Binding Protein 1
D000941:Antigens; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; C064655:V(D)J recombination activating protein 2; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse