Effects of the complement system on antibody formation and function: implications for transplantation.
Journal
Current opinion in organ transplantation
ISSN: 1531-7013
Titre abrégé: Curr Opin Organ Transplant
Pays: United States
ID NLM: 9717388
Informations de publication
Date de publication:
01 10 2022
01 10 2022
Historique:
pubmed:
21
7
2022
medline:
16
9
2022
entrez:
20
7
2022
Statut:
ppublish
Résumé
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. 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. 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.
Identifiants
pubmed: 35857345
doi: 10.1097/MOT.0000000000001002
pii: 00075200-202210000-00007
pmc: PMC9474663
mid: NIHMS1819156
doi:
Substances chimiques
Isoantibodies
0
Complement System Proteins
9007-36-7
Types de publication
Journal Article
Review
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
399-404Subventions
Organisme : NIAID NIH HHS
ID : R01 AI141434
Pays : United States
Informations de copyright
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
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