T Cell Mediated Conversion of a Non-Anti-La Reactive B Cell to an Autoreactive Anti-La B Cell by Somatic Hypermutation.
3T3 Cells
Adoptive Transfer
Amino Acid Sequence
Animals
Antibody Specificity
/ genetics
Autoantibodies
/ chemistry
Autoantigens
/ chemistry
Autoimmune Diseases
/ genetics
Autoimmunity
/ genetics
B-Lymphocytes
/ immunology
Cell Communication
/ immunology
Disease Models, Animal
Epitope Mapping
Epitopes
/ chemistry
Fluorescent Antibody Technique
Germ Cells
/ metabolism
Humans
Immunization
Mice
Mice, Transgenic
Models, Molecular
Protein Conformation
Ribonucleoproteins
/ chemistry
Somatic Hypermutation, Immunoglobulin
T-Lymphocytes
/ immunology
SS-B Antigen
La/SS-B autoantigen
anti-La/SS-B antibodies
autoimmunity
primary Sjögren’s syndrome
systemic lupus erythematosus
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
26 Jan 2021
26 Jan 2021
Historique:
received:
29
12
2020
revised:
20
01
2021
accepted:
22
01
2021
entrez:
3
2
2021
pubmed:
4
2
2021
medline:
14
4
2021
Statut:
epublish
Résumé
Since the first description of nuclear autoantigens in the late 1960s and early 1970s, researchers, including ourselves, have found it difficult to establish monoclonal antibodies (mabs) against nuclear antigens, including the La/SS-B (Sjögrens' syndrome associated antigen B) autoantigen. To date, only a few anti-La mabs have been derived by conventional hybridoma technology; however, those anti-La mabs were not bona fide autoantibodies as they recognize either human La specific, cryptic, or post-translationally modified epitopes which are not accessible on native mouse La protein. Herein, we present a series of novel murine anti-La mabs including truly autoreactive ones. These mabs were elicited from a human La transgenic animal through adoptive transfer of T cells from non-transgenic mice immunized with human La antigen. Detailed epitope and paratope analyses experimentally confirm the hypothesis that somatic hypermutations that occur during T cell dependent maturation can lead to autoreactivity to the nuclear La/SS-B autoantigen.
Identifiants
pubmed: 33530489
pii: ijms22031198
doi: 10.3390/ijms22031198
pmc: PMC7865296
pii:
doi:
Substances chimiques
Autoantibodies
0
Autoantigens
0
Epitopes
0
Ribonucleoproteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIH HHS
ID : GM63497
Pays : United States
Organisme : Oklahoma Center for the Advancement of Science and Technology OK, USA
ID : HR01-003
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