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The Journal of Immunology, Vol 149, Issue 1 60-64, Copyright © 1992 by American Association of Immunologists
ARTICLES |
CL Schultz, P Rothman, R Kuhn, M Kehry, W Muller, K Rajewsky, F Alt and RL Coffman
Department of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304-1104.
Studies using plasma membranes from activated Th cell clones (Th membranes) to stimulate B cells have shown that both a contact-mediated activation signal plus Th-derived cytokines are required for antibody production. In order to clearly separate and define the role of these two signals in isotype switching, B cells were stimulated with Th membranes in the presence or absence of cytokines, and the transcriptional activity of the unrearranged H chain loci was determined. In the presence of Th membranes, two known switch factors were shown to specifically induce germ-line transcription of the same H chain loci as in LPS-stimulated B cells (IL-4 induced C gamma 1 and C epsilon transcription, transforming growth factor-beta induced C alpha transcription). The contact-mediated activation signal provided by the Th membranes, in the absence of any added cytokines, resulted in the specific induction of C gamma 1 germ-line transcription, and thus functioned as a switch signal for IgG1. These findings provide a mechanism for previously observed IL-4-independent isotype switching to IgG1.
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