An Interleukin-2 Signal Relieves BSAP (Pax5)-Mediated Repression of the Immunoglobulin J Chain Gene

• Published in: Immunity (Cambridge, Mass.) Mass.), 1996-10, Vol.5 (4), p.377-386
• Main Authors: Rinkenberger, Julie L, Wallin, Jeffrey J, Johnson, Kirk W, Koshland, Marian Elliott
• Format: Article
• Language: English
• Subjects: Animals; B-Lymphocytes - physiology; Cell Differentiation; Cells, Cultured; DNA-Binding Proteins - physiology; Gene Expression Regulation; Genes, Immunoglobulin; Immunoglobulin J-Chains - genetics; Interleukin-2 - physiology; Mice; Nuclear Proteins - physiology; PAX5 Transcription Factor; Promoter Regions, Genetic; Repressor Proteins - physiology; Sequence Deletion; Transcription Factors
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/S1074-7613(00)80263-0

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 downstream 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.