Cellular competition independent of BAFF/B lymphocyte stimulator results in low frequency of an autoreactive clonotype in mature polyclonal B cell compartments.
J Immunol
; 187(1): 37-46, 2011 Jul 01.
Article
en En
| MEDLINE
| ID: mdl-21632709
ABSTRACT
The peripheral B cell prosurvival cytokine BAFF/B lymphocyte stimulator (BLyS) has been proposed to participate in the regulation of immunological tolerance. Selective elimination or reconstitution of B cells expressing transgene-encoded, autoreactive BCRs upon systemic BLyS depletion or supplementation, respectively, was observed in two separate studies. Such findings led to a model positing a higher dependency of autoreactive B cells on BLyS. We tested this model by exploiting two targeted IgH transgenic mice (H chain knock-in [HKI]) that produce large numbers of follicular (FO) B cells that are either weakly or strongly autoreactive with nuclear autoantigens. Even though HKI B cells do not exhibit classical features of anergy, we found that mature, naive, autoreactive HKI B cells are outcompeted for representation in the periphery by a polyclonal B cell population. However, this is not due to a higher dependency of HKI B cells on BLyS for survival. Additionally, excess BLyS does not rescue HKI B cells from selective elimination. These findings suggest that some autoreactive FO B cells can fully develop while in competition with non-autoreactive cells for BLyS, but remain at a competitive disadvantage for other trophic factors that regulate peripheral stability. As such, our data indicate the existence of peripheral tolerance mechanisms that regulate the frequency of autoreactive FO B cells independent of the BLyS pathway.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Autoantígenos
/
Diferenciación Celular
/
Subgrupos de Linfocitos B
/
Anergia Clonal
/
Factor Activador de Células B
/
Linfopenia
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Immunol
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos