Guidance of B Cells by the Orphan G Protein-Coupled Receptor EBI2 Shapes Humoral Immune Responses

SummaryHumoral immunity depends on both rapid and long-term antibody production against invading pathogens. This is achieved by the generation of spatially distinct extrafollicular plasmablast and follicular germinal center (GC) B cell populations, but the signals that guide responding B cells to these alternative compartments have not been fully elucidated. Here, we show that expression of the orphan G protein-coupled receptor Epstein-Barr virus-induced gene 2 (EBI2, also known as GPR183) by activated B cells was essential for their movement to extrafollicular sites and induction of early plasmablast responses. Conversely, downregulation of EBI2 enabled B cells to access the center of follicles and promoted efficient GC formation. EBI2 therefore provides a previously uncharacterized dimension to B cell migration that is crucial for coordinating rapid versus long-term antibody responses

Complement receptors regulate differentiation of bone marrow plasma cell precursors expressing transcription factors Blimp-1 and XBP-1

Humoral immune responses are thought to be enhanced by complement-mediated recruitment of the CD21–CD19–CD81 coreceptor complex into the B cell antigen receptor (BCR) complex, which lowers the threshold of B cell activation and increases the survival and proliferative capacity of responding B cells. To investigate the role of the CD21–CD35 complement receptors in the generation of B cell memory, we analyzed the response against viral particles derived from the bacteriophage Qβ in mice deficient in CD21–CD35 (Cr2−/−). Despite highly efficient induction of early antibody responses and germinal center (GC) reactions to immunization with Qβ, Cr2−/− mice exhibited impaired antibody persistence paralleled by a strongly reduced development of bone marrow plasma cells. Surprisingly, antigen-specific memory B cells were essentially normal in these mice. In the absence of CD21-mediated costimulation, Qβ-specific post-GC B cells failed to induce the transcriptional regulators Blimp-1 and XBP-1 driving plasma cell differentiation, and the antiapoptotic protein Bcl-2, which resulted in failure to generate the precursor population of long-lived plasma cells residing in the bone marrow. These results suggest that complement receptors maintain antibody responses by delivery of differentiation and survival signals to precursors of bone marrow plasma cells

B cell priming for extrafollicular antibody responses requires Bcl-6 expression by T cells

Bcl-6 expression in CD4+ T cells is required to generate extrafollicular antibody responses

Impaired Embryonic Development in Mice Overexpressing the RNA-Binding Protein TIAR

TIA-1-related (TIAR) protein is a shuttling RNA-binding protein involved in several steps of RNA metabolism. While in the nucleus TIAR participates to alternative splicing events, in the cytoplasm TIAR acts as a translational repressor on specific transcripts such as those containing AU-Rich Elements (AREs). Due to its ability to assemble abortive pre-initiation complexes coalescing into cytoplasmic granules called stress granules, TIAR is also involved in the general translational arrest observed in cells exposed to environmental stress. However, the in vivo role of this protein has not been studied so far mainly due to severe embryonic lethality upon tiar invalidation.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Civiltà della Campania. Anno I, n. 1 (dicembre 1974)

A.I, n. 1 (dicembre 1974): M. Parrilli, Editoriale, P. 3 ; R. Virtuoso, Civiltà della Campania, P. 3 ; G. Galasso, Fisionomìa storica della regione, P. 6 ; Natale in Campania, P. 11, R. Causa, Cinque secoli di Presepe di, P. 12 ; M. Stefanile, I presepi d’una volta di, P. 20 ; D. Rea, L’universo mangereccio del Presepe di, P. 28 ; M. Prisco, Il presepe in provincia di, P. 34 ; B. Gatta, Una storia che non fu, P. 42 ; A. Mozzillo, Stendhal a Napoli, P. 47 ; E. Perrin, Viaggio a Cava d’un abate francese, P. 52 ; A.P. Carbone, Ravello: Villa Rufolo un paradiso per tutti, 54 ; D. Fernandez, Lettera d’amore a Napoli, P. 60 ; A. Gatto, Un mazzetto di poesie con la mia mano, 54 ; M. Parrilli, Vocazione turistica e culturale del Salernitano, P. 60 ; E. Comito, Poesia di Casertantica, P. 64 ; A. Fratta, Majorca e le Sirene, P. 67 ; V. Ricciuti, De Sica addio, P. 72 ; M. Perrotta, Il motoscafo spazzino del mare di Capri, P. 76 ; F. Canessa, Ritorna l’« opera buffa », P. 78 ; P. Gargano, Archeologia in villa, P. 83 ; E. Corsi, Per un nuovo equilibrio alberghiero, P. 86 ; F. Garbaccio, Un termalismo per tutte le stagioni, P. 88; G. Blasi, Amalfi by night, P. 90 ; A. Scelzo, La maratona Paestum-Salerno, P. 91 ; Notiziario, P. 92 ; F. De Ciuceis, Segnalazioni bibliografiche, P. 95

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Une nécropole de type Chamblandes à Thonon-les-Bains (Haute-Savoie). Un premier état des lieux

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