An interleukin-2 signal relieves BSAP (Pax5)-mediated repression of the immunoglobulin J chain gene.
Cytokine regulation of B cell development was analyzed using interleukin-2 (IL-2)-induced transcription of the J chain gene as a model system. A nuclear target of the IL-2 signal was identified as the Pax5 transcription factor, BSAP, which recognizes a negative regulatory motif in the J chain promoter. Functional assays showed that BSAP mediates the silencing of the J chain gene during the early stages of B cell development, but repression is relieved during the antigen-driven stages in a concentration-dependent manner by an IL-2-induced down-regulation of BSAP RNA expression. At the low levels present in J chain-expressing plasma cells, BSAP repression could be overridden by positive-acting factors binding to down-stream J chain promoter elements. Overexpression of BSAP in these cells reversed the positive regulation and inhibited J chain gene transcription. Thus, IL-2 regulation of BSAP concentration may provide a mechanism for controlling both repressor and activator functions of BSAP during a B cell immune response.
Rinkenberger
J L
JL
Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
Wallin
J J
JJ
Johnson
K W
KW
Koshland
M E
ME
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D005803:Genes, Immunoglobulin; D007144:Immunoglobulin J-Chains / Q000235:genetics*; D007376:Interleukin-2 / Q000502:physiology*; D051379:Mice; D009687:Nuclear Proteins / Q000502:physiology*; D051757:PAX5 Transcription Factor; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000502:physiology*; D017384:Sequence Deletion; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D007144:Immunoglobulin J-Chains; D007376:Interleukin-2; D009687:Nuclear Proteins; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors