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

Dessislava Malinova*, Laabiah Wasim, Rebecca Newman, Ana Martínez‐Riaño, Niklas Engels, Pavel Tolar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

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.
Original languageEnglish
Pages (from-to)e51328
JournalEMBO Reports
Early online date29 Jul 2021
DOIs
Publication statusEarly online date - 29 Jul 2021

Keywords

  • EMBO19
  • EMBO20
  • Article
  • Articles
  • antigen uptake
  • B‐cell responses
  • endocytosis
  • endophilin A2
  • germinal center

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