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2 results on '"Lelouard H"'

1. Progressively impaired proteasomal capacity during terminal plasma cell differentiation

Author

Cenci, S., Mezghrani, A., Cascio, P., Bianchi, G., Cerruti, F., Fra, A., Lelouard, H., Masciarelli, S., Mattioli, L., Oliva, L., Orsi, A., Pasqualetto, E., Pierre, P., Ruffato, E., Tagliavacca, L., Sitia, R., Cenci, S., Mezghrani, A., Cascio, P., Bianchi, G., Cerruti, F., Fra, A., Lelouard, H., Masciarelli, S., Mattioli, L., Oliva, L., Orsi, A., Pasqualetto, E., Pierre, P., Ruffato, E., Tagliavacca, L., and Sitia, R.

Abstract

After few days of intense immunoglobulin (Ig) secretion, most plasma cells undergo apoptosis, thus ending the humoral immune response. We asked whether intrinsic factors link plasma cell lifespan to Ig secretion. Here we show that in the late phases of plasmacytic differentiation, when antibody production becomes maximal, proteasomal activity decreases. The excessive load for the reduced proteolytic capacity correlates with accumulation of poly-ubiquitinated proteins, stabilization of endogenous proteasomal substrates (including Xbp1s, IκBα, and Bax), onset of apoptosis, and sensitization to proteasome inhibitors (PI). These events can be reproduced by expressing Ig-μ chain in nonlymphoid cells. Our results suggest that a developmental program links plasma cell death to protein production, and help explaining the peculiar sensitivity of normal and malignant plasma cells to PI. ©2006 European Molecular Biology Organization.

Published
2006

2. Transient aggregation of ubiquitinated proteins during dendritic cell maturation.

Author

Lelouard H, Gatti E, Cappello F, Gresser O, Camosseto V, and Pierre P

Subjects
Animals, Antigen Presentation, Canavanine pharmacology, Catalytic Domain, Cysteine Endopeptidases chemistry, Cysteine Endopeptidases metabolism, Cytoplasm metabolism, Dendritic Cells drug effects, Dendritic Cells immunology, Histocompatibility Antigens Class I biosynthesis, Histocompatibility Antigens Class I immunology, Lipopolysaccharides pharmacology, Male, Mice, Mice, Inbred C57BL, Multienzyme Complexes chemistry, Multienzyme Complexes metabolism, Nocodazole pharmacology, Oligopeptides pharmacology, Proteasome Endopeptidase Complex, Protein Binding drug effects, Protein Biosynthesis, Protein Denaturation, Protein Subunits, Protein Transport drug effects, Cell Differentiation drug effects, Dendritic Cells cytology, Dendritic Cells metabolism, Histocompatibility Antigens Class I metabolism, Ubiquitin metabolism
Abstract

Dendritic cells (DCs) are antigen-presenting cells with the unique capacity to initiate primary immune responses. Dendritic cells have a remarkable pattern of differentiation (maturation) that exhibits highly specific mechanisms to control antigen presentation restricted by major histocompatibility complex (MHC). MHC class I molecules present to CD8(+) cytotoxic T cells peptides that are derived mostly from cytosolic proteins, which are ubiquitinated and then degraded by the proteasome. Here we show that on inflammatory stimulation, DCs accumulate newly synthesized ubiquitinated proteins in large cytosolic structures. These structures are similar to, but distinct from, aggresomes and inclusion bodies observed in many amyloid diseases. Notably, these dendritic cell aggresome-like induced structures (DALIS) are transient, require continuous protein synthesis and do not affect the ubiquitin-proteasome pathway. Our observations suggest the existence of an organized prioritization of protein degradation in stimulated DCs, which is probably important for regulating MHC class I presentation during maturation.

Published
2002
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