T cell mediated antibody invariance in an immune response against a bacterial carbohydrate antigen requires CD28/B7-1 costimulation.
The humoral immune response against alpha(1-->3) dextran (Dex) in BALB/c mice is characterized by the formation of predominantly IgM antibodies bearing the J558 idiotype. IgG antibodies do not appear in euthymic mice. In athymic animals however, the response proceeds to a vigorous IgG production. In euthymic mice formation of IgG is suppressed by J558 idiotype-specific regulatory T cells recognizing in association with I-Ed and in cognate T/B interaction the VH CDR3 derived peptide of the J558 idiotpye. Only B-2 lymphocytes produce IgG whereas B-1 cells do not participate in the production of this Ig class. Using a novel synthetic all alpha(1-->3)-D-gluco configurated tetrasaccharide the Dex-specific B cells can for the first time be analyzed in FACS. In experiments using this newly designed low molecular Dex no signs of B cell apoptosis can be found. This demonstrates a true silencing of persisting Bgamma memory cells and supports previous by adoptive transfer experiments. In this suppression an involvement of CD28/B7-1 interaction can be demonstrated which is a necessary costimulatory suppression signal in addition to the cognate TCR/peptide-I-Ed interaction between J558 Id-specific T cells and J558 idiotype bearing B cells. This results in an activation of 178-4 Ts cells, leading to an overall suppression of the Dex-specific IgG isotype production on the one hand and on the other hand provides a signal for the survival and clonal expansion of J558 Id-positive B cells.
Rademaekers
A
A
Institute for Immunology, University of Münster, Germany. rademae@uni-muenster.de
Kölsch
E
E
Specht
C
C
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology*; D017209:Apoptosis; D018122:B7-1 Antigen / Q000378:metabolism*; D018106:CD28 Antigens / Q000378:metabolism*; D018929:Cell Culture Techniques; D022801:Complementarity Determining Regions / Q000276:immunology; D003911:Dextrans / Q000276:immunology; D008211:Lymphocyte Cooperation; D051379:Mice; D008807:Mice, Inbred BALB C; D018448:Models, Immunological; D010950:Plasma Cells / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000907:Antibodies, Bacterial; D018122:B7-1 Antigen; D018106:CD28 Antigens; D022801:Complementarity Determining Regions; D003911:Dextrans; D011135:Polysaccharides, Bacterial; C040834:alpha-1,3-dextran