REGULATORY MECHANISMS THAT DETERMINE THE DEVELOPMENT AND FUNCTION OF PLASMA CELLS
摘要:
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.
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关键词:
Animals Humans Mice Germinal Center Transcription Factors Repressor Proteins DNA-Binding Proteins Membrane Proteins Proto-Oncogene Proteins Nuclear Proteins
DOI:
10.1146/annurev.immunol.21.120601.141138
被引量:
年份:
2003






























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