Positive and negative selection shape the human naive B cell repertoire.
J Clin Invest
; 132(2)2022 01 18.
Article
em En
| MEDLINE
| ID: mdl-34813502
ABSTRACT
Although negative selection of developing B cells in the periphery is well described, yet poorly understood, evidence of naive B cell positive selection remains elusive. Using 2 humanized mouse models, we demonstrate that there was strong skewing of the expressed immunoglobulin repertoire upon transit into the peripheral naive B cell pool. This positive selection of expanded naive B cells in humanized mice resembled that observed in healthy human donors and was independent of autologous thymic tissue. In contrast, negative selection of autoreactive B cells required thymus-derived Tregs and MHC class II-restricted self-antigen presentation by B cells. Indeed, both defective MHC class II expression on B cells of patients with rare bare lymphocyte syndrome and prevention of self-antigen presentation via HLA-DM inhibition in humanized mice resulted in the production of autoreactive naive B cells. These latter observations suggest that Tregs repressed autoreactive naive B cells continuously produced by the bone marrow. Thus, a model emerged, in which both positive and negative selection shaped the human naive B cell repertoire and that each process was mediated by fundamentally different molecular and cellular mechanisms.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
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Antígenos de Histocompatibilidade Classe II
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Imunodeficiência Combinada Severa
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Linfócitos T Reguladores
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Apresentação de Antígeno
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
J Clin Invest
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos