Selective activation of naïve B cells with unique epitope specificity shapes autoantibody formation in celiac disease.
J Autoimmun
; 146: 103241, 2024 Jun.
Article
in En
| MEDLINE
| ID: mdl-38754235
ABSTRACT
Many antibody responses induced by infection, vaccination or autoimmunity show signs of convergence across individuals with epitope-dependent selection of particular variable region gene segments and complementarity determining region 3 properties. However, not much is known about the relationship between antigen-specific effector cells and antigen-specific precursors present in the naïve B-cell repertoire. Here, we sought to address this relationship in the context of celiac disease, where there is a stereotyped autoantibody response against the enzyme transglutaminase 2 (TG2). By generating TG2-specific monoclonal antibodies from both duodenal plasma cells and circulating naïve B cells, we demonstrate a discord between the naïve TG2-specific repertoire and the cells that are selected for autoantibody production. Hence, the naïve repertoire does not fully reflect the epitope preference and gene usage observed for memory B cells and plasma cells. Instead, distinct naïve B cells that target particular TG2 epitopes appear to be selectively activated at the expense of TG2-binding B cells targeting other epitopes.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Autoantibodies
/
B-Lymphocytes
/
Lymphocyte Activation
/
Celiac Disease
/
Transglutaminases
/
Epitopes, B-Lymphocyte
/
GTP-Binding Proteins
/
Protein Glutamine gamma Glutamyltransferase 2
Limits:
Adult
/
Female
/
Humans
/
Male
Language:
En
Journal:
J Autoimmun
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: