title: Regulatory mechanisms that determine the development and function of plasma cells.
abstract: 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.
authors.affiliation: Department of Microbiology and Biochemistry, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA. klc1@columbia.edu
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Calame
authors.forename: Kuo-I
authors.initials: KI
authors.lastname: Lin
authors.forename: Chainarong
authors.initials: C
authors.lastname: Tunyaplin
mesh_terms: 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
chemical_list: 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