Regulatory mechanisms that determine the development and function of plasma cells

Annu Rev Immunol. 2003;21:205-30. doi: 10.1146/annurev.immunol.21.120601.141138. Epub 2001 Dec 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Antibody Formation
  • B-Lymphocyte Subsets / cytology
  • B-Lymphocyte Subsets / immunology
  • Cell Differentiation
  • Cell Division
  • DNA-Binding Proteins / metabolism
  • Germinal Center / cytology
  • Germinal Center / immunology
  • Humans
  • Interferon Regulatory Factors
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism
  • Mice
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • PAX5 Transcription Factor
  • Plasma Cells / cytology*
  • Plasma Cells / immunology*
  • Plasma Cells / metabolism
  • Positive Regulatory Domain I-Binding Factor 1
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-6
  • Regulatory Factor X Transcription Factors
  • Repressor Proteins / metabolism
  • Transcription Factors / metabolism
  • X-Box Binding Protein 1

Substances

  • DNA-Binding Proteins
  • Interferon Regulatory Factors
  • Membrane Proteins
  • NFATC Transcription Factors
  • Nuclear Proteins
  • PAX5 Transcription Factor
  • PAX5 protein, human
  • Pax5 protein, mouse
  • Prdm1 protein, mouse
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-6
  • Regulatory Factor X Transcription Factors
  • Repressor Proteins
  • Transcription Factors
  • X-Box Binding Protein 1
  • XBP1 protein, human
  • Xbp1 protein, mouse
  • interferon regulatory factor-4
  • PRDM1 protein, human
  • Positive Regulatory Domain I-Binding Factor 1