The Journal of Immunology, Vol 154, Issue 10 5136-5143, Copyright © 1995 by American Association of Immunologists

ARTICLES

Up-regulation of recombination activating gene expression by signal transduction through the surface Ig receptor

LK Verkoczy, BJ Stiernhdm and NL Berinstein
Department of Immunology, University of Toronto, Ontario, Canada.

Recent evidence has demonstrated that a signal transduced through the lymphocyte Ag receptor may regulate the expression of the recombination activating genes (RAG). Although several groups have shown that such a signal may be required to down-regulate RAG-1 and RAG-2 after a functional Ag receptor has been generated in early mature T or B cells, recently it has been suggested that under some circumstances, cross- linking the B cell Ag receptor may result in up-regulation of RAG expression. To study this possibility, we used a unique set of cell variants isolated from a human mature B cell line, which differ in their expression of both the surface Ig receptor (sIg) and RAG-1 and RAG-2 genes. Two forms of stimulation were employed to generate a signal; either a soluble F(ab')2 anti-mu fragment or the combination of PMA and ionomycin. Northern blot analysis demonstrated that RAG-1 mRNA levels were increased in sIg+ variants after cross-linking with anti- mu. Increases were also observed in all variants after stimulation with PMA and ionomycin. Further analysis of cross-linked sIg+ variants suggests that the observed up-regulation in RAG expression was a reversible event. Furthermore, we have determined that both increased transcription and transcript stabilization contributed to this inducible up-regulation. We thus describe a mature B cell line in which RAG expression is up-regulated after sIg cross-linking. This finding is discussed in the context of its potential role in situations where sIg+ B cells may undergo secondary rearrangements for the purpose of "editing" their sIg receptors.

This article has been cited by other articles:

				L. Bai, Y. Chen, Y. He, X. Dai, X. Lin, R. Wen, and D. Wang Phospholipase C{gamma}2 Contributes to Light-Chain Gene Activation and Receptor Editing Mol. Cell. Biol., September 1, 2007; 27(17): 5957 - 5967. [Abstract] [Full Text] [PDF]

				H. Wulff, H.-G. Knaus, M. Pennington, and K. G. Chandy K+ Channel Expression during B Cell Differentiation: Implications for Immunomodulation and Autoimmunity J. Immunol., July 15, 2004; 173(2): 776 - 786. [Abstract] [Full Text] [PDF]

				M. Hikida, M. Mori, T. Takai, K.-i. Tomochika, K. Hamatani, and H. Ohmori Reexpression of RAG-1 and RAG-2 Genes in Activated Mature Mouse B cells Science, December 20, 1996; 274(5295): 2092 - 2094. [Abstract] [Full Text]

				L. K. Verkoczy, B.-a. Guinn, and N. L. Berinstein Characterization of the Human B Cell RAG-associated Gene, hBRAG, as a B Cell Receptor Signal-enhancing Glycoprotein Dimer That Associates with Phosphorylated Proteins in Resting B Cells J. Biol. Chem., July 7, 2000; 275(28): 20967 - 20979. [Abstract] [Full Text] [PDF]