21.[20220910]Effects of the complement system on antibody formation an…
2022-Effects of the complement system on antibody formation and function_impli.pdf
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Review Curr Opin Organ Transplant
. 2022 Oct 1;27(5):399-404. doi: 10.1097/MOT.0000000000001002. Epub 2022 Jul 15.
Effects of the complement system on antibody formation and function: implications for transplantation
Arun Cumpelik 1, Peter S Heeger
Affiliations expand
PMID: 35857345 PMCID: PMC9474663 (available on 2023-10-01) DOI: 10.1097/MOT.0000000000001002
Abstract
Purpose of review: In antibody-mediated allograft rejection, donor-reactive antibodies cause transplant injury in part via complement activation. New mechanistic insights indicate complement also modulates development of humoral immune responses. Herein we review recent data that describes how complement affects antibody formation and we discuss therapeutic implications.
Recent findings: Extravasating T cells interacting with integrins express and activate intracellular complement that drives immune-metabolic adaptations vital for CD4 + helper cells. Marginal zone B cells can acquire intact major histocompatibility complexes from dendritic cells via complement-dependent trogocytosis for presentation to T cells. Activated B cells in germinal centers receive co-stimulatory signals from T-helper cells. These germinal center B cells undergo coordinate shifts in surface complement regulator expression that permit complement receptor signaling on the germinal center B cells required for affinity maturation. The positively selected, high-affinity B cells can differentiate into plasma cells that produce donor-HLA-reactive antibodies capable of ligating endothelial, among other, graft cells. Subsequent sublytic complement attack can stimulate endothelial cells to activate CD4 + and CD8 + T cells, promoting cellular and humoral rejection. Newly developed complement inhibitors are being tested to prevent/treat transplant rejection.
Summary: The complement system influences T-cell, B-cell and endothelial-cell activation, and thereby contributes allograft injury. Emerging therapeutic strategies targeting complement activation have the potential to prevent or abrogate transplant injury and improve transplant outcomes.
Review Curr Opin Organ Transplant
. 2022 Oct 1;27(5):399-404. doi: 10.1097/MOT.0000000000001002. Epub 2022 Jul 15.
Effects of the complement system on antibody formation and function: implications for transplantation
Arun Cumpelik 1, Peter S Heeger
Affiliations expand
PMID: 35857345 PMCID: PMC9474663 (available on 2023-10-01) DOI: 10.1097/MOT.0000000000001002
Abstract
Purpose of review: In antibody-mediated allograft rejection, donor-reactive antibodies cause transplant injury in part via complement activation. New mechanistic insights indicate complement also modulates development of humoral immune responses. Herein we review recent data that describes how complement affects antibody formation and we discuss therapeutic implications.
Recent findings: Extravasating T cells interacting with integrins express and activate intracellular complement that drives immune-metabolic adaptations vital for CD4 + helper cells. Marginal zone B cells can acquire intact major histocompatibility complexes from dendritic cells via complement-dependent trogocytosis for presentation to T cells. Activated B cells in germinal centers receive co-stimulatory signals from T-helper cells. These germinal center B cells undergo coordinate shifts in surface complement regulator expression that permit complement receptor signaling on the germinal center B cells required for affinity maturation. The positively selected, high-affinity B cells can differentiate into plasma cells that produce donor-HLA-reactive antibodies capable of ligating endothelial, among other, graft cells. Subsequent sublytic complement attack can stimulate endothelial cells to activate CD4 + and CD8 + T cells, promoting cellular and humoral rejection. Newly developed complement inhibitors are being tested to prevent/treat transplant rejection.
Summary: The complement system influences T-cell, B-cell and endothelial-cell activation, and thereby contributes allograft injury. Emerging therapeutic strategies targeting complement activation have the potential to prevent or abrogate transplant injury and improve transplant outcomes.
