Activation-Induced Cytidine Deaminase Impacts the Primary Antibody Repertoire in Naive Mice.
J Immunol
; 208(12): 2632-2642, 2022 06 15.
Article
em En
| MEDLINE
| ID: mdl-35675956
ABSTRACT
Genetic and environmental cues shape the evolution of the B cell Ig repertoire. Activation-induced cytidine deaminase (AID) is essential to generating Ig diversity through isotype class switching and somatic mutations, which then directly influence clonal selection. Impaired B cell development in AID-knockout mice has made it difficult to study Ig diversification in an aging repertoire. Therefore, in this report, we used a novel inducible AID-knockout mouse model and discovered that deleting AID in adult mice caused spontaneous germinal center formation. Deep sequencing of the IgH repertoire revealed that Ab diversification begins early in life and evolves over time. Our data suggest that activated B cells form germinal centers at steady state and facilitate continuous diversification of the B cell repertoire. In support, we identified shared B cell lineages that were class switched and showed age-dependent rates of mutation. Our data provide novel context to the genesis of the B cell repertoire that may benefit the understanding of autoimmunity and the strength of an immune response to infection.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Switching de Imunoglobulina
/
Citidina Desaminase
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2022
Tipo de documento:
Article