The impact of H2-DM on humoral immune responses.
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.
Alfonso
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C
R. W. Johnson Pharmaceutical Research Institute, San Diego, CA 92121, USA.
Han
J O
JO
Williams
G S
GS
Karlsson
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L
D000818:Animals; D000915:Antibody Affinity / Q000235:genetics; D000917:Antibody Formation / Q000235:genetics; D017951:Antigen Presentation / Q000235:genetics; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018858:Germinal Center / Q000276:immunology / Q000473:pathology; D006183:H-2 Antigens / Q000096:biosynthesis / Q000235:genetics; D006681:HLA-D Antigens / Q000235:genetics / Q000502:physiology*; D006241:Haptens / Q000008:administration & dosage / Q000276:immunology; D006433:Hemocyanins / Q000008:administration & dosage / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006825:Hybridomas; D007074:Immunoglobulin G / Q000096:biosynthesis; D007274:Injections, Intraperitoneal; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009113:Muramidase / Q000008:administration & dosage / Q000276:immunology; D009596:Nitrophenols / Q000008:administration & dosage / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010648:Phenylacetates; D011961:Receptors, Fc / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D019076:Transgenes / Q000276:immunology
D006183:H-2 Antigens; C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D006241:Haptens; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D009596:Nitrophenols; D010446:Peptide Fragments; D010648:Phenylacetates; D011961:Receptors, Fc; C026242:4-hydroxy-5-nitrophenyl acetic acid; D010047:Ovalbumin; D006433:Hemocyanins; C421864:hen egg lysozyme; D009113:Muramidase; C032808:keyhole-limpet hemocyanin