ACTIVATION OF B-CELLS BY 1 MU-M PARTICULATE LYSOZYME OR PEPTIDES - A T-H-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, bas ed on covalent linkage of proteins or peptides to 1 mu m latex particl es and showed that these antigens cannot be presented to MHC class Ii- restricted specific T cells by B cells, However, they induce strong CD 4(+) T cell responses when injected to mice without adjuvant. The pres ent study demonstrates that four out of the five proteins tested did n ot stimulate antibody synthesis when linked to 1 mu m microparticles, although a strong IgG production was induced by the same proteins admi nistered in soluble form with adjuvant. In contrast, lysozyme and two synthetic peptides containing B and T cell viral epitopes induced stro ng and long-lasting specific antibody responses when linked to 1 mu m synthetic beads. The isotypic pattern of antibodies induced by particu late lysozyme was similar to that induced by the soluble protein in al um. Studies using CD4(+) T cell-depleted mice revealed that the induct ion of antibodies by particulate lysozyme strictly required T-h cell a ctivity. Moreover, the T-B cell cooperation involved in a cell activat ion by antigens linked to beads required CD40-CD40 ligand interaction. Thus, these particulate antigens provide a useful tool to study the m echanisms of induction of antibody response against complex bacterial or parasitic antigens. Moreover, they may represent attractive candida tes to elaborate efficient new vaccines using short synthetic peptides .