Regulation of antibody isotype secretion by subsets of antigen-specific helper T cells.
The regulation of the subclass of immunoglobulin secreted by B cells has been studied in vitro in polyclonal systems using mitogens, such as lipopolysaccharide (LPS), to bypass the requirement for cognate interaction between antigen-specific T and B cells. In these systems, interleukin-(IL)-4 induces the secretion of IgG1 (ref. 1) and IgE (ref. 2); IL-5 enhances the secretion of IgA, and interferon-gamma (IFN-gamma) enhances the secretion of IgG2a (ref. 5). Clones of murine TH cells can be divided into two subsets, TH1 and TH2 (ref. 6). Both subsets synthesize IL-3 and granulocyte-monocyte colony-stimulating factor (GM-CSF), but only TH1 clones produce IL-2, IFN-gamma, and lymphotoxin (LT) and TH2 clones produce IL-4 and IL-5 (ref. 7). We have examined the role of clones of antigen-specific TH1 and TH2 cells in the regulation of the subclasses of IgG antibody secreted by antigen-specific B cells. Our results show that both types of TH cells induce the secretion of IgM and IgG3, whereas clones of TH1 and TH2 cells specifically induce antigen-specific B cells to secrete IgG2a and IgG1, respectively. We also demonstrate that regulation of commitment to the secretion of a particular IgG isotype occurs in two distinct stages: cognate interaction between T and B cells and interaction between T-cell-derived lymphokines and B cells.
Stevens
T L
TL
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.
Bossie
A
A
Sanders
V M
VM
Fernandez-Botran
R
R
Coffman
R L
RL
Mosmann
T R
TR
Vitetta
E S
ES
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D000939:Epitopes; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4; D007378:Interleukins / Q000494:pharmacology; D008211:Lymphocyte Cooperation; D008222:Lymphokines / Q000502:physiology; D051379:Mice; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014301:Trinitrobenzenes / Q000276:immunology
D000939:Epitopes; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007376:Interleukin-2; D007378:Interleukins; D008222:Lymphokines; D014301:Trinitrobenzenes; D015847:Interleukin-4; D007371:Interferon-gamma