Regulatory mechanisms that determine the development and function of plasma cells.
Plasma cells are terminally differentiated final effectors of the humoral immune response. Plasma cells that result from antigen activation of B-1 and marginal zone B cells provide the first, rapid response to antigen. Plasma cells that develop after a germinal center reaction provide higher-affinity antibody and often survive many months in the bone marrow. Transcription factors Bcl-6 and Pax5, which are required for germinal center B cells, block plasmacytic differentiation and repress Blimp-1 and XBP-1, respectively. When Bcl-6-dependent repression of Blimp-1 is relieved, Blimp-1 ensures that plasmacytic development is irreversible by repressing BCL-6 and PAX5. In plasma cells, Blimp-1, XBP-1, IRF4, and other regulators cause cessation of cell cycle, decrease signaling from the B cell receptor and communication with T cells, inhibit isotype switching and somatic hypermutation, downregulate CXCR5, and induce copious immunoglobulin synthesis and secretion. Thus, commitment to plasmacytic differentiation involves inhibition of activities associated with earlier B cell developmental stages as well as expression of the plasma cell phenotype.
Calame
Kathryn L
KL
Department of Microbiology and Biochemistry, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA. klc1@columbia.edu
Lin
Kuo-I
KI
Tunyaplin
Chainarong
C
D000818:Animals; D000917:Antibody Formation; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000378:metabolism; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D006801:Humans; D050835:Interferon Regulatory Factors; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D051757:PAX5 Transcription Factor; D010950:Plasma Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6; D000071701:Regulatory Factor X Transcription Factors; D012097:Repressor Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000071717:X-Box Binding Protein 1; D000099218:Interferon Regulatory Factor-4
D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D008565:Membrane Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D051757:PAX5 Transcription Factor; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D000071701:Regulatory Factor X Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; D000099218:Interferon Regulatory Factor-4; C497281:PAX5 protein, human; C497282:Pax5 protein, mouse; C513258:Prdm1 protein, mouse; C000605543:XBP1 protein, human; C000605544:Xbp1 protein, mouse; C087042:PRDM1 protein, human