T helper cell membranes promote IL-4-independent expression of germ-line C gamma 1 transcripts in B cells.
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.
Schultz
C L
CL
Department of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304-1104.
Rothman
P
P
Kühn
R
R
Kehry
M
M
Müller
W
W
Rajewsky
K
K
Alt
F
F
Coffman
R L
RL
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
D007127:Immunoglobulin Constant Regions; D007074:Immunoglobulin G; D007142:Immunoglobulin gamma-Chains; D012333:RNA, Messenger; D015847:Interleukin-4