Induction of germ-line immunoglobulin heavy chain transcripts by mitogens and interleukins prior to switch recombination
Department of Molecular Genetics and Microbiology
Animals; DNA Probes; Female; Gene Expression Regulation; Immunoglobulin Heavy Chains; Immunoglobulin Isotypes; Immunoglobulin Switch Region; Immunologic Deficiency Syndromes; Interferon Type II; Interleukin-4; Interleukin-5; Kinetics; Lipopolysaccharides; Male; Mice; Poly A; RNA Probes; RNA, Messenger; Recombination, Genetic; Spleen
Life Sciences | Medicine and Health Sciences | Women's Studies
It has recently been postulated that immunoglobulin class switching is preceded by transcription from unrearranged heavy chain genes. In this report, we have investigated the conditions under which RNA transcribed from unrearranged C gamma 3, C gamma 1, C gamma 2b, C gamma 2a, C epsilon and C alpha genes are induced in normal spleen cells by mitogens and/or interleukin (IL) 4, IL 5 and interferon-gamma. Lipopolysaccharide (LPS) plus IL 4 induced germ-line gamma 1 and epsilon transcripts. LPS induced gamma 2b and gamma 3 transcripts and high doses of IL 4 suppressed these LPS-induced transcripts. Interferon-gamma induced low levels of germ-line gamma 2a transcripts and profoundly suppressed the gamma 1 and epsilon transcripts induced by LPS and IL 4. IL 5 alone or in combination with IL 4 and/or LPS did not induce germ-line alpha transcripts. Spleen cells of the partially immunodeficient mice CBA/N and C3H/HeJ, which do not express IgG3 could be induced, however, by polyclonal activators to express germ-line gamma 3 and gamma 2b transcripts. The data indicate that the capacity of a ligand to induce/suppress transcription of a particular unrearranged heavy chain gene is a good indicator of its capacity to induce switching to the corresponding Ig isotype. However, it is also clear that control of switching can be carried out at other levels.
Rights and Permissions
Citation: Eur J Immunol. 1990 May;20(5):1079-84.