title: Antigen-unspecific B cells and lymphoid dendritic cells both show extensive surface expression of processed antigen-major histocompatibility complex class II complexes after soluble protein exposure in vivo or in vitro.
abstract: Intravenous (i.v.) injection of high amounts of soluble proteins often results in the induction of antigen-specific tolerance or deviation to helper rather than inflammatory T cell immunity. It has been proposed that this outcome may be due to antigen presentation to T cells by a large cohort of poorly costimulatory or IL-12-deficient resting B cells lacking specific immunoglobulin receptors for the protein. However, previous studies using T cell activation in vitro to assess antigen display have failed to support this idea, showing evidence of specific peptide-major histocompatibility complex (MHC) class II ligand only on purified dendritic cells (DC) or antigen-specific B cells isolated from protein injected mice. Here we reexamine this question using a recently derived monoclonal antibody specific for the T cell receptor (TCR) ligand formed by the association of the 46-61 determinant of hen egg lysozyme (HEL) and the mouse MHC class II molecule I-Ak. In striking contrast to conclusions drawn from indirect T cell activation studies, this direct method of TCR ligand analysis shows that i.v. administration of HEL protein results in nearly all B cells in lymphoid tissues having substantial levels of HEL 46-61-Ak complexes on their surface. DC readily isolated from spleen also display this TCR ligand on their surface. Although the absolute number of displayed ligands is greater on such DC, the relative specific ligand expression compared to total MHC class II levels is similar or greater on B cells. These results demonstrate that in the absence of activating stimuli, both lymphoid DC and antigen-unspecific B cells present to a similar extent class II-associated peptides derived from soluble proteins in extracellular fluid. The numerical advantage of the TCR ligand-bearing B cells may permit them to interact first or more often with naive antigen-specific T cells, contributing to the induction of high-dose T cell tolerance or immune deviation.
authors.affiliation: Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1892, USA.
authors.forename: G
authors.initials: G
authors.lastname: Zhong
authors.forename: C
authors.initials: C
authors.lastname: Reis e Sousa
authors.forename: R N
authors.initials: RN
authors.lastname: Germain
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007150:Immunohistochemistry; D008024:Ligands; D008198:Lymph Nodes / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D009113:Muramidase / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D012710:Serum Albumin, Bovine / Q000276:immunology; D012995:Solubility; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D012710:Serum Albumin, Bovine; D009113:Muramidase