Endophilin A2 regulates B-cell endocytosis and is required for germinal center and humoral responses.
EMBO Rep
; 22(9): e51328, 2021 09 06.
Article
em En
| MEDLINE
| ID: mdl-34323351
ABSTRACT
Antigen-specific B-cell responses require endosomal trafficking to regulate antigen uptake and presentation to helper T cells, and to control expression and signaling of immune receptors. However, the molecular composition of B-cell endosomal trafficking pathways and their specific roles in B-cell responses have not been systematically investigated. Here, we report high-throughput identification of genes regulating B-cell receptor (BCR)-mediated antigen internalization using genome-wide functional screens. We show that antigen internalization depends both on constitutive, clathrin-mediated endocytosis and on antigen-induced, clathrin-independent endocytosis mediated by endophilin A2. Although endophilin A2-mediated endocytosis is dispensable for antigen presentation, it is selectively required for metabolic support of B-cell proliferation, in part through regulation of iron uptake. Consequently, endophilin A2-deficient mice show defects in GC B-cell responses and production of high-affinity IgG. The requirement for endophilin A2 highlights a unique importance of clathrin-independent intracellular trafficking in GC B-cell clonal expansion and antibody responses.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Clatrina
/
Endocitose
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article