Picogram quantities of anti-Ig antibodies coupled to dextran induce B cell proliferation.
To investigate the properties which enable type 2 Ag, as exemplified by dextran and Ficoll, to stimulate high levels of antibody responses in the relative absence of T cells, we conjugated anti-IgD and anti-IgM mAb to both dextran and Ficoll and examined their B cell-activating properties. Such conjugated anti-Ig antibodies stimulated both early and later stages of B cell activation at picogram concentrations, which are at least 1000-fold lower than that required for B cell stimulation by unconjugated anti-Ig antibodies, and the level of proliferation they stimulated was on average 10-fold greater. Furthermore, concentrations of anti-Ig dextran (100 pg/ml) which modulated little sIgD from the B cell surface were strong inducers of enhanced B cell expression of MHC class II molecules. Conjugation of Fab fragments of anti-IgD or nonmitogenic anti-IgM mAb to dextran rendered them as mitogenic as dextran conjugated to strongly stimulatory anti-IgD or anti-IgM antibodies. The ability of dextran and Ficoll to serve as effective carrier molecules for anti-IgD was not related solely to their large m.w., because anti-IgD coupled to polymerized BSA (m.w. 1.5 X 10(6), was only 10- to 50-fold more potent than unconjugated anti-IgD antibodies at stimulating B cell DNA synthesis. These results suggest, therefore, that the unique ability of picogram concentrations of haptenated type 2 Ag to stimulate Ig secretion in the absence of T cells may be a function of their ability to promote effective cross-linking without resulting in the modulation of sIg. This would enable such Ag to mediate repetitive B cell signaling, a situation that cannot be achieved by unconjugated anti-Ig antibodies which result in modulation of sIg at their mitogenic concentrations. These compounds therefore may be employed to study B cell activation stimulated by sIg cross-linking at concentrations that may more closely reflect those which are achieved under physiologic conditions by type 2 Ag.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000032:analysis / Q000502:physiology*; D000954:Antigens, Surface / Q000032:analysis; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology* / Q000494:pharmacology; D003432:Cross-Linking Reagents; D003911:Dextrans / Q000276:immunology* / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007072:Immunoglobulin D / Q000032:analysis / Q000276:immunology* / Q000502:physiology; D007140:Immunoglobulin Fab Fragments / Q000502:physiology; D007075:Immunoglobulin M / Q000276:immunology / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008934:Mitogens / Q000502:physiology; D008970:Molecular Weight; D011108:Polymers; D012710:Serum Albumin, Bovine / Q000276:immunology / Q000494:pharmacology
D000888:Antibodies, Anti-Idiotypic; D000954:Antigens, Surface; D002352:Carrier Proteins; D003432:Cross-Linking Reagents; D003911:Dextrans; D000949:Histocompatibility Antigens Class II; D007072:Immunoglobulin D; D007140:Immunoglobulin Fab Fragments; D007075:Immunoglobulin M; D008934:Mitogens; D011108:Polymers; C039951:anti-IgD; C044203:anti-IgM; D012710:Serum Albumin, Bovine