Abstract
H2-DM (DM, previously H2-M) facilitates the exchange of peptides bound to MHC class II molecules. In this study, we have used H2-DM-deficient (DM(-/-)) mice to analyze the influence of DM in the priming of B cell responses in vivo and for Ag presentation by B cells in vitro. After immunization, IgG Abs could be raised to a T-dependent Ag, 4-hydroxy-5-nitrophenylacetyl-OVA, in DM(-/-) mice, but closer analysis revealed the IgG response to be slower, diminished in titer, and composed of low-affinity Abs. The Ab response correlated with a vast reduction in the number of germinal centers in the spleen. The presentation of multiple epitopes by H2-A(b) from distinct Ags was found to be almost exclusively DM-dependent whether B cells internalized Ags via fluid phase uptake or using membrane Ig receptors. The poor B cell response in vivo could be largely, but not completely restored by expression of a H2-Ea(d) transgene, despite the fact that Ag presentation by H2-E(d/b) molecules was found to be highly DM dependent. Hence, while substantial Ab responses can be raised in the absence of DM, this molecule is a crucial factor both for Ag processing and for the normal maturation of T-dependent humoral immune responses in vivo.
MeSH terms
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Animals
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Antibody Affinity / genetics
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Antibody Formation* / genetics
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Antigen Presentation / genetics
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B-Lymphocyte Subsets / immunology
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B-Lymphocyte Subsets / metabolism
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Germinal Center / immunology
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Germinal Center / pathology
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H-2 Antigens / biosynthesis
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H-2 Antigens / genetics
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HLA-D Antigens / genetics
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HLA-D Antigens / physiology*
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Haptens / administration & dosage
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Haptens / immunology
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Hemocyanins / administration & dosage
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Hemocyanins / immunology
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Histocompatibility Antigens Class II / biosynthesis
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Histocompatibility Antigens Class II / genetics
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Histocompatibility Antigens Class II / physiology*
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Hybridomas
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Immunoglobulin G / biosynthesis
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Injections, Intraperitoneal
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Mice
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Mice, Knockout
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Mice, Transgenic
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Muramidase / administration & dosage
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Muramidase / immunology
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Nitrophenols / administration & dosage
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Nitrophenols / immunology
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Ovalbumin / administration & dosage
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Ovalbumin / immunology
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Peptide Fragments / genetics
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Peptide Fragments / immunology
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Peptide Fragments / metabolism
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Phenylacetates
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Receptors, Fc / physiology
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T-Lymphocytes / immunology
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Transgenes / immunology
Substances
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H-2 Antigens
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H2-M antigens
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HLA-D Antigens
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HLA-DM antigens
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Haptens
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Histocompatibility Antigens Class II
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Immunoglobulin G
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Nitrophenols
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Peptide Fragments
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Phenylacetates
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Receptors, Fc
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4-hydroxy-5-nitrophenyl acetic acid
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Ovalbumin
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Hemocyanins
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hen egg lysozyme
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Muramidase
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keyhole-limpet hemocyanin