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• W4385235005 abstract "B cell maturation in germinal centers (GCs) depends on cognate interactions between the T and B cells. Upon interaction with CD40 ligand (CD40L) on T cells, CD40 delivers co-stimulatory signals alongside B cell antigen receptor (BCR) signaling to regulate affinity maturation and antibody class-switch during GC reaction. Mutations in CD40L disrupt interactions with CD40, which lead to abnormal antibody responses in immune deficiencies known as X-linked Hyper IgM syndrome (X-HIgM). Assuming that physical interactions between highly mobile T and B cells generate mechanical forces on CD40-CD40L bonds, we set out to study the B cell mechanobiology mediated by CD40-CD40L interaction. Using a suite of biophysical assays we find that CD40 forms catch bond with CD40L where the bond lasts longer at larger forces, B cells exert tension on CD40-CD40L bonds, and force enhances CD40 signaling and antibody class-switch. Significantly, X-HIgM CD40L mutations impair catch bond formation, suppress endogenous tension, and reduce force-enhanced CD40 signaling, leading to deficiencies in antibody class switch. Our findings highlight the critical role of mechanotransduction in CD40 function and provide insights into the molecular mechanisms underlying X-HIgM syndrome." @default.
• W4385235005 created "2023-07-26" @default.
• W4385235005 creator A5023211409 @default.
• W4385235005 creator A5033369558 @default.
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• W4385235005 creator A5049893048 @default.
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• W4385235005 creator A5092537467 @default.
• W4385235005 date "2023-07-25" @default.
• W4385235005 modified "2023-09-25" @default.
• W4385235005 title "Mechanotransduction governs CD40 function and underlies X-linked Hyper IgM syndrome" @default.
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