Activation-induced cytidine deaminase (AID) expression in human B-cell precursors is essential for central B-cell tolerance

Autor: Jolan E. Walter, Renee Wu, Shigeaki Nonoyama, Anne Durandy, Yen Shing Ng, Jean Nicolas Schickel, Jason M. Bannock, Eric Meffre, Tyler Oe, Hans D. Ochs, Christopher Massad, Waleed Al-Herz, Tineke Cantaert, Luigi D. Notarangelo, Sara Sebnem Kilic, Aubert Lavoie
Přispěvatelé: Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Anabilim Dalı., AAH-1658-2021, Kılıç, Sara Şebnem
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Male
Mouse
Apoptosis
B lymphocyte tolerance
Lymphocyte Activation
Mice
Pre B lymphocyte
Receptors
B cell development
Mechanisms
Activation-induced (cytidine) deaminase
Immunology and Allergy
Enzyme activity
Child
Priority journal
Recombination
Genetic
education.field_of_study
Genes
Immunoglobulin
Nuclear Proteins
Immunological tolerance
Activation induced cytidine deaminase
Cytidine deaminase
Middle Aged
3. Good health
Cell biology
DNA-Binding Proteins
Enzyme inhibition
Infectious Diseases
medicine.anatomical_structure
B cell tolerance
AID-deficient patients
Child
Preschool
Central Tolerance
Deficiency
Translocations
Female
Antibody
Central tolerance
Short hairpin RNA
Animal cell
Human
Gene dosage
Adult
AICDA (Activation-induced Cytidine Deaminase)
Cytidine Deaminase
DNA
Adolescent
Immunoglobulin gene
Bcl6
activation-induced cytidine deaminase
Immunology
Population
Nuclear protein
Case control study
Somatic hypermutation
Biology
Article
Young Adult
Fetus
Aıid expression
RAG2
V(d)j recombination
Genetics
medicine
Animals
Humans
Bone marrow
Human tissue
Cell clone
education
B cell
Aged
P53
Genetic recombination
RAG2 protein
human
Animal
Precursor Cells
B-Lymphoid
RAG2 protein
Newborn
Nonhuman
DNA binding protein
Human cell
Preschool child
Case-Control Studies
biology.protein
Protein expression
Somatic Hypermutation
Immunoglobulin
Cell maturation
Class-switch recombination
Controlled study
Cell function
Popis: Activation-induced cytidine deaminase (AID), the enzyme- mediating class-switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes, is essential for the removal of developing autoreactive B cells. How AID mediates central B cell tolerance remains unknown. We report that AID enzymes were produced in a discrete population of immature B cells that expressed recombination-activating gene 2 (RAG2), suggesting that they undergo secondary recombination to edit autoreactive antibodies. However, most AID(+) immature B cells lacked anti-apoptotic MCL-1 and were deleted by apoptosis. AID inhibition using lentiviral-encoded short hairpin (sh)RNA in B cells developing in humanized mice resulted in a failure to remove autoreactive clones. Hence, B cell intrinsic AID expression mediates central B cell tolerance potentially through its RAG-coupled genotoxic activity in self-reactive immature B cells. United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Allergy & Infectious Diseases (NIAID) (AI061093) United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Allergy & Infectious Diseases (NIAID) (AI071087) United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Allergy & Infectious Diseases (NIAID) (AI082713) INSERM, CEE EUROPAD-contract 7th Framework Program (201549) Assiociation Contre le Cancer Rubicon program, Netherlands Organization for Scientific Research United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Allergy & Infectious Diseases (NIAID) (R01AI071087) United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Allergy & Infectious Diseases (NIAID) (P01AI061093) United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Allergy & Infectious Diseases (NIAID) (U19AI082713)
Databáze: OpenAIRE
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