期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 38, 期 3, 页码 658-667出版社
WILEY
DOI: 10.1002/eji.200737743
关键词
antibodies; apoptosis; B cells; cell differentiation; proteasomes
类别
资金
- Telethon [GGP06155] Funding Source: Medline
- Associazione Italiana per la Ricerca sul Cancro Funding Source: Custom
Upon encounter with Ag, B lymphocytes undergo terminal differentiation into plasma cells, highly specialized Ab secretors that mediate humoral immune responses. Profound changes adapt cellular morphology and proteome to the new secretory functions. Although a massive secretory activity is expected to require an efficient ubiquitin-proteasome degradation system, recent in vitro studies have surprisingly revealed that the proteasome function sharply decreases during plasma cell development, thereby limiting the proteolytic capacity. We challenged this paradigm in mouse models of B cell activation, and observed that following polyclonal activation, proteasome activity decreases more than previously reported in vitro. This decrease is linked to enhanced apoptosis after treatment with the potent anti-myeloma proteasome inhibitor PS-341. Accordingly, in vivo treatment with PS-341 decreases Ab titres in T-dependent and -independent mouse immunization models. This study provides the rationale for limiting the activity of Ab-secreting cells in vivo by impacting proteasome function.
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