Loss of tolerance of anti-dsDNA B cells in mice overexpressing CD19.
Mol Immunol
; 43(11): 1776-90, 2006 Apr.
Article
em En
| MEDLINE
| ID: mdl-16430962
ABSTRACT
Mice transgenic for the R4A-Cmu heavy chain of an anti-dsDNA antibody, maintain tolerance by anergy and deletion. In C57BL/6 mice overexpressing CD19, a molecule, which lowers the threshold for B cell activation, elevated levels of serum autoantibodies have been observed. In the present study, we wished to determine whether CD19 overexpression could alter the induction of tolerance in R4A-Cmu mice and lead to the secretion of transgenic anti-dsDNA antibodies. We, therefore, bred R4A-Cmu transgenic mice-to-mice transgenic for human CD19 (hCD19) and generated R4A-Cmu mice heterozygous and homozygous for hCD19. We, now report the spontaneous secretion of transgenic IgM anti-dsDNA antibody in the sera of R4A-Cmu mice overexpressing CD19, indicative of a loss of B cell tolerance. We observe that transgenic B cells secreting anti-dsDNA antibody in these mice are T independent and display a marginal zone like phenotype althought they do not reside in the MZ. In addition, they appear to be derived from the conventional B2 subset rather than the B1 subset. Interestingly, a subset of the anti-dsDNA B cells in these mice still display the phenotype and functional characteristics of anergic B cells. These B cells cannot be activated to secrete antibody following BCR crosslinking, however, they are hyper-responsive to activation by innate signaling mechanisms. This suggests that CD19 overexpression may promote anergic B cells to escape tolerance by converging with BCR independent pathways, thereby rendering these B cells hyper-responsive to innate signaling.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA
/
Subpopulações de Linfócitos B
/
Antígenos CD19
/
Tolerância Imunológica
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Immunol
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos