Malinova, D;
Wasim, L;
Newman, R;
Martinez-Riano, A;
Engels, N;
Tolar, P;
(2021)
Endophilin A2 regulates B-cell endocytosis and is required for germinal center and humoral responses.
EMBO Reports
, Article e51328. 10.15252/embr.202051328.
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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.
| Type: | Article |
|---|---|
| Title: | Endophilin A2 regulates B-cell endocytosis and is required for germinal center and humoral responses |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.15252/embr.202051328 |
| Publisher version: | https://doi.org/10.15252/embr.202051328 |
| Language: | English |
| Additional information: | Copyright © 2021 The Authors. Published under the terms of the CC BY 4.0 license. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | antigen uptake, B-cell responses, endocytosis, endophilin A2, germinal center |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10133037 |
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