Unknown

Dataset Information

0

Endophilin A2 regulates B-cell endocytosis and is required for germinal center and humoral responses.


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.

SUBMITTER: Malinova D 

PROVIDER: S-EPMC8419706 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC6538628 | biostudies-literature
| S-EPMC7725609 | biostudies-literature
| S-EPMC6327748 | biostudies-literature
| S-EPMC8344742 | biostudies-literature
| S-EPMC4863967 | biostudies-literature
| S-EPMC5225073 | biostudies-literature
| S-EPMC10625619 | biostudies-literature
| S-EPMC6996002 | biostudies-literature
| S-EPMC7224292 | biostudies-literature
| S-EPMC3268296 | biostudies-other