The isotype of an Ig-containing mediator dictates the isotype of the antibody produced: a novel mechanism of isotype regulation.
Within 6 hours after primary immunization the serum of mice contains a unique form of processed antigen which is complexed with immunoglobulin (Ig). These complexes are formed through the mediation of a T cell factor and markedly enhance in vivo the 7s antibody response. They possess potent antisuppressor activity, i.e., they reverse suppression to immunity both in vivo and in vitro. We have been able to generate in vitro complexes containing a single Ig isotype. Such complexes returned the antibody formation in a suppressed culture only for the same Ig isotype as that present in the complexes. Thus, complexes containing IgG2a, induced exclusively IgG2a antibody and those containing IgA returned only the IgA response in the suppressed culture. The selection of a particular isotype for the formation of the complexes is determined by inducer T cells that produce the factor. The spleen contains inducer T cells capable of mediating the formation of complexes with IgG2a or IgA, while the T cells from Peyer's patches can induce the formation only of IgA complexes. The formation of the complexes is the earliest response to antigen in vivo and, according to the data presented here, the type of isotypes to be synthesized during an immune response may be determined as early as 3-6 hours after immunization as a result of the formation of these isotype specific complexes.
Lee
S T
ST
Department of Internal Medicine, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Maeba
J
J
Ernst
P B
PB
Bienenstock
J
J
Paraskevas
F
F
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology* / Q000378:metabolism; D004912:Erythrocytes / Q000276:immunology; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D008954:Models, Biological; D012756:Sheep / Q000097:blood; D013601:T-Lymphocytes / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000941:Antigens; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes