Activation of B cells by 1 microm particulate lysozyme or peptides: a Th-dependent pathway requiring CD40-CD40 ligand interaction.
Many antigens encountered by the immune system are included in complex structures such as bacteria or parasites. We previously developed an in vivo model to study the immunogenicity of particulate antigens, based on covalent linkage of proteins or peptides to 1 microm latex particles and showed that these antigens cannot be presented to MHC class II-restricted specific T cells by B cells. However, they induce strong CD4+ T cell responses when injected to mice without adjuvant. The present study demonstrates that four out of the five proteins tested did not stimulate antibody synthesis when linked to 1 microm microparticles, although a strong IgG production was induced by the same proteins administered in soluble form with adjuvant. In contrast, lysozyme and two synthetic peptides containing B and T cell viral epitopes induced strong and long-lasting specific antibody responses when linked to 1 micrometer synthetic beads. The isotypic pattern of antibodies induced by particulate lysozyme was similar to that induced by the soluble protein in alum. Studies using CD4+ T cell-depleted mice revealed that the induction of antibodies by particulate lysozyme strictly required Th cell activity. Moreover, the T-B cell cooperation involved in B cell activation by antigens linked to beads required CD40-CD40 ligand interaction. Thus, these particulate antigens provide a useful tool to study the mechanisms of induction of antibody response against complex bacterial or parasitic antigens. Moreover, they may represent attractive candidates to elaborate efficient new vaccines using short synthetic peptides.
Unité de Biologie des Régulations Immunitaires, Institut Pasteur, Paris, France.
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Sedlik
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Rojas
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Leclerc
D000536:Aluminum Hydroxide / Q000276:immunology; D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism*; D023201:CD40 Ligand; D002478:Cells, Cultured; D000939:Epitopes / Q000276:immunology; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008863:Microspheres; D009113:Muramidase / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D012995:Solubility; D013154:Spleen / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D013997:Time Factors
D019013:CD40 Antigens; D000939:Epitopes; D008562:Membrane Glycoproteins; D010455:Peptides; D023201:CD40 Ligand; D000536:Aluminum Hydroxide; D006433:Hemocyanins; D009113:Muramidase