Negligible class II MHC presentation of B cell receptor-derived peptides by high density resting B cells.
Resting B lymphocytes have been credited with inducing T cell tolerance to Ig-derived and monovalent self-Ags that are internalized via the B cell receptor (BCR). These conclusions are predicated upon the assumptions that resting B cells display BCR-associated peptides in class II MHC and that the cells remain quiescent during the course of experimental manipulation. To determine whether resting B cells display BCR-associated epitopes in class II MHC, we devised a sensitive assay that averted potential activation of B cells by Ag and minimized activation by prolonged culture. Ex vivo, Percoll-fractionated B cells expressing a kappa transgene encoding a T cell epitope were cultured with a reactive T cell hybridoma for 12 h. Whereas low density, LPS-activated, and BCR-activated B cells elicited significant IL-2 from the T cell hybridoma, resting high density B cells did not. Parallel results were obtained with normal B cells expressing a second epitope encoded by an endogenous V(H) gene. Anergic B cells, which are uniformly low density, also significantly stimulated the T cell hybridoma. Finally, longer culture periods with normal B cells resulted in a higher degree of B cell activation and significant stimulation of reactive T cell hybridomas. Our results provide evidence that activation of B cells profoundly enhances the processing and presentation of BCR-associated Ags.
Snyder
Christopher M
CM
Integrated Department of Immunology, University of Colorado School of Medicine and National Jewish Medical and Research Center, Denver, CO 80206, USA.
Zhang
Xianghua
X
Wysocki
Lawrence J
LJ
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002452:Cell Count; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D017635:Clonal Anergy; D018920:Coculture Techniques; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D016056:Immunodominant Epitopes / Q000096:biosynthesis / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000378:metabolism; D007145:Immunoglobulin kappa-Chains / Q000096:biosynthesis / Q000378:metabolism; D016130:Immunophenotyping; D007399:Interphase / Q000276:immunology*; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D010446:Peptide Fragments; D011947:Receptors, Antigen, B-Cell