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

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. © 2021 The Authors. Published under the terms of the CC BY 4.0 license.

Citation

Dessislava Malinova, Laabiah Wasim, Rebecca Newman, Ana Martínez-Riaño, Niklas Engels, Pavel Tolar. Endophilin A2 regulates B-cell endocytosis and is required for germinal center and humoral responses. EMBO reports. 2021 Sep 06;22(9):e51328

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PMID: 34323351

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