MHC class II/T-cell receptor interactions potentiate secretion of IgG but not IgM in response to T-dependent antigens.
We have examined whether the interaction of peptide-loaded MHC molecules on the surface of B-cells with antigen-specific T-cell receptors (TCRs) enhances Ig secretion in the presence of other antigen-independent interactions in vitro. B-cells specific for region 25-40 of beta-lactoglobulin (beta-LG) were stimulated in a T-cell dependent manner using plasma membranes (PM) derived from two different T-helper (Th) clones, culture supernatants of activated Th2 cells and beta-LG as a specific antigen. PM were obtained from either the beta-LG-specific T-cell clone H1.1 which can mediate specific TCR/MHC class II interactions as well as antigen-independent ones or from the D10 clone which bears a TCR of an irrelevant specificity and thus, can only mediate antigen-independent interactions. IgG, but not IgM, secretion was specifically enhanced by H1.1 PM, but not D10 PM in the presence of beta-LG. Furthermore, a blockade of TCR/MHC class II interactions using either anti-T-cell receptor, beta or anti-CD4 monoclonal antibodies inhibited this enhanced IgG secretion in response to beta-LG. The results show that while antigen-independent interactions between T- and B-cells can enhance secretion of IgM antibodies, specific interactions between TCRs and peptide:MHC complexes stimulate B-cells to enhance secretion of IgG but not IgM antibodies. This mechanism may contribute to antibody secretion only from B-cells activated through cognate interaction in vivo.
Takahashi
Y
Y
Department of Applied Biological Chemistry, The University of Tokyo, Japan.
Ametani
A
A
Totsuka
M
M
Fujine
K
K
Tsuji
N M
NM
Kurisaki
J
J
Kaminogawa
S
S
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015704:CD4 Antigens / Q000276:immunology; D002460:Cell Line; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007074:Immunoglobulin G / Q000378:metabolism*; D007075:Immunoglobulin M / Q000378:metabolism*; D007782:Lactoglobulins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*
D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007782:Lactoglobulins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta