Induction of the Igκ 3′ enhancer by distinct pathways can be inhibited by cross‐linking of the CD40 receptor

• Published in: European journal of immunology 1999-03, Vol.29 (3), p.872-877
• Main Author: Meyer, Kerstin B.
• Format: Article
• Language: English
• Subjects: CD40; Immunoglobulin enhancer; Transcription
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/(SICI)1521-4141(199903)29:03<872::AID-IMMU872>3.0.CO;2-X

Upon treatment with lipopolysaccharide (LPS), primary B cells proliferate and differentiate into plasma cells with concomitant up‐regulation of immunoglobulin (Ig) gene expression. Here we examine the role of the Igκ 3′ enhancer in this process using a κ3′‐enhancer‐driven β‐globin reporter gene in transgenic mice. We find that LPS treatment up‐regulates κ3′ enhancer activity as a function of differentiation rather than proliferation, since proliferation only (induced by cross‐linking of CD40) is insufficient to activate the element, whilst differentiation with only limited proliferation (LPS + transforming growth factor‐β) does allow activation to occur. The Igκ 3′ enhancer is also induced by cross‐linking of surface Ig and this signal can synergize with LPS activation, suggesting that distinct activation pathways are used. Nevertheless, both of these pathways can be inhibited by co‐cross‐linking of CD40. Thus Ig enhancers in the heavy and light chain loci are differentially regulated in response to CD40.