Fine tuning of IRF-4 expression by SWAP-70 controls the initiation of plasma cell development

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Michaël Chopin - , Medical Faculty Carl Gustav Carus (Author)
  • Carlos Andrés Chacón Martínez - , Medical Faculty Carl Gustav Carus (Author)
  • Rolf Jessberger - , Institute of Physiological Chemistry (Author)

Abstract

The generation of plasma cells (PCs) is key for proper humoral immune responses. The transcription factors IRF-4 and BLIMP-1 (B-lymphocyte induce maturation protein-1) control PC commitment, but the underlying regulatory mechanisms are incompletely understood. Here we have identified SWAP-70 as being critically involved in Toll-like receptor (TLR)-triggered PC differentiation. Upon activation through various TLRs, Swap-70(-/-) B cells were activated and proliferated normally. However, expression of BLIMP-1 was markedly reduced and PC differentiation was impaired. Four hours of LPS stimulation were sufficient to drive PC differentiation, and SWAP-70 was required during this initial period. Swap-70(-/-) B cells pre-activated in vitro failed to efficiently differentiate into PCs upon adoptive transfer into recipient mice. Re-introduction of SWAP-70 into Swap-70(-/-) B cells rescued their development into PCs, and SWAP-70 over-expression in wild-type (WT) B cells increased PC generation. In the absence of SWAP-70, IRF-4 protein levels were reduced and the IRF-4(high) B220(+) CD138(-) compartment, including PC precursors, was strongly diminished. Ectopic expression of SWAP-70 increases IRF-4 protein levels and PC differentiation in WT and Swap-70(-/-) B cells, and IRF-4 over-expression in Swap-70(-/-) B cells elevates PC differentiation to WT levels. Thus, in a dose-dependent manner, SWAP-70 controls IRF-4 protein expression and thereby regulates the initiation of PC differentiation.

Details

Original languageEnglish
Pages (from-to)3063-3074
Number of pages12
JournalEuropean Journal of Immunology
Volume41
Issue number10
Publication statusPublished - Oct 2011
Peer-reviewedYes

External IDs

Scopus 80053135256
PubMed 21728176

Keywords

Keywords

  • Animals, Antibodies, Monoclonal, B-Lymphocytes/metabolism, Cell Differentiation, DNA-Binding Proteins/metabolism, Guanine Nucleotide Exchange Factors/metabolism, Immunity, Humoral, Immunoblotting, Interferon Regulatory Factors/biosynthesis, Lipopolysaccharides/pharmacology, Lymphocyte Activation, Mice, Mice, Knockout, Minor Histocompatibility Antigens, Nuclear Proteins/metabolism, Plasma Cells/cytology, Polymerase Chain Reaction, Positive Regulatory Domain I-Binding Factor 1, Toll-Like Receptors/immunology, Transcription Factors/biosynthesis