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1.
Nat Immunol ; 23(7): 1076-1085, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35761085

RESUMO

Memory B cells persist for a lifetime and rapidly differentiate into antibody-producing plasmablasts and plasma cells upon antigen re-encounter. The clonal relationship and evolution of memory B cells and circulating plasmablasts is not well understood. Using single-cell sequencing combined with isolation of specific antibodies, we found that in two healthy donors, the memory B cell repertoire was dominated by large IgM, IgA and IgG2 clonal families, whereas IgG1 families, including those specific for recall antigens, were of small size. Analysis of multiyear samples demonstrated stability of memory B cell clonal families and revealed that a large fraction of recently generated plasmablasts was derived from long-term memory B cell families and was found recurrently. Collectively, this study provides a systematic description of the structure, stability and dynamics of the human memory B cell pool and suggests that memory B cells may be active at any time point in the generation of plasmablasts.


Assuntos
Células B de Memória , Plasmócitos , Linfócitos B , Células Cultivadas , Humanos , Imunoglobulina G , Memória Imunológica
2.
J Neurosci Res ; 98(11): 2263-2274, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33174240

RESUMO

Convergent lines of evidence have recently highlighted ß3-adrenoreceptors (ARs) as a potentially critical target in the regulation of nervous and behavioral functions, including memory consolidation, anxiety, and depression. Nevertheless, the role of ß3-ARs in the cerebellum has been never investigated. To address this issue, we first examined the effects of pharmacological manipulation of ß3-ARs on motor learning in mice. We found that blockade of ß3-ARs by SR 59230A impaired the acquisition of the rotarod task with no effect on general locomotion. Since the parallel fiber-Purkinje cell (PF-PC) synapse is considered to be the main cerebellar locus of motor learning, we assessed ß3-AR modulatory action on this synapse as well as its expression in cerebellar slices. We demonstrate, for the first time, a strong expression of ß3-ARs on Purkinje cell soma and dendrites. In addition, whole-cell patch-clamp recordings revealed that bath application of ß3-AR agonist CL316,243 depressed the PF-PC excitatory postsynaptic currents via a postsynaptic mechanism mediated by the PI3K signaling pathway. Application of CL316,243 also interfered with the expression of PF long-term potentiation, whereas SR 59230A prevented the induction of LTD at PF-PC synapse. These results underline the critical role of ß3-AR on cerebellar synaptic transmission and plasticity and provide a new mechanism for adrenergic modulation of motor learning.


Assuntos
Córtex Cerebelar/fisiologia , Receptores Adrenérgicos beta 3/fisiologia , Transmissão Sináptica/fisiologia , Animais , Córtex Cerebelar/metabolismo , Potenciais Pós-Sinápticos Excitadores , Feminino , Potenciação de Longa Duração , Depressão Sináptica de Longo Prazo , Masculino , Camundongos , Plasticidade Neuronal/fisiologia , Técnicas de Patch-Clamp , Fosfatidilinositol 3-Quinases/metabolismo , Células de Purkinje/metabolismo , Receptores Adrenérgicos beta 3/metabolismo , Teste de Desempenho do Rota-Rod , Sinapses/fisiologia
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