Idiotype-specific Th cells support oligoclonal expansion of anti-dsDNA B cells in mice with lupus.
J Immunol
; 193(6): 2691-8, 2014 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-25127856
ABSTRACT
Systemic lupus erythematosus (SLE) is marked by a Th cell-dependent B cell hyperresponsiveness, with frequent germinal center reactions and hypergammaglobulinemia. The specificity of Th cells in lupus remains unclear, but B cell Ids have been suggested. A hallmark is the presence of anti-dsDNA, mutated IgG autoantibodies with a preponderance of arginines in CDR3 of the Ig variable H chain (IgVH). B cells can present V region-derived Id peptides on their MHC class II molecules to Id-specific Th cells. We show that Id-specific Th cells support the proliferation of anti-dsDNA Id(+) B cells in mice suffering from systemic autoimmune disease with SLE-like features. Mice developed marked clonal expansions of B cells; half of the IgVH sequences were clonally related. Anti-dsDNA B cells made up 40% of B cells in end-stage disease. The B cells expressed mutated IgVH with multiple arginines in CDR3. Hence, Id-driven T cell-B cell collaboration supported the production of classical anti-dsDNA Abs, recapitulating the characteristics of such Abs in SLE. The results support the concept that Id-specific Th cells may trigger the development of SLE and suggest that manipulation of the Id-specific T cell repertoire could play a role in treatment.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
DNA
/
Anticorpos Antinucleares
/
Linfócitos T Auxiliares-Indutores
/
Seleção Clonal Mediada por Antígeno
/
Lúpus Eritematoso Sistêmico
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article