title: T helper cell membranes promote IL-4-independent expression of germ-line C gamma 1 transcripts in B cells.
abstract: 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.
authors.affiliation: Department of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304-1104.
authors.forename: C L
authors.initials: CL
authors.lastname: Schultz
authors.forename: P
authors.initials: P
authors.lastname: Rothman
authors.forename: R
authors.initials: R
authors.lastname: Kühn
authors.forename: M
authors.initials: M
authors.lastname: Kehry
authors.forename: W
authors.initials: W
authors.lastname: Müller
authors.forename: K
authors.initials: K
authors.lastname: Rajewsky
authors.forename: F
authors.initials: F
authors.lastname: Alt
authors.forename: R L
authors.initials: RL
authors.lastname: Coffman
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002450:Cell Communication; D002462:Cell Membrane / Q000502:physiology; D005786:Gene Expression Regulation; D005803:Genes, Immunoglobulin; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007074:Immunoglobulin G / Q000235:genetics*; D007142:Immunoglobulin gamma-Chains / Q000235:genetics*; D015847:Interleukin-4 / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000648:ultrastructure; D014158:Transcription, Genetic
chemical_list: D007127:Immunoglobulin Constant Regions; D007074:Immunoglobulin G; D007142:Immunoglobulin gamma-Chains; D012333:RNA, Messenger; D015847:Interleukin-4