New insights into immune mechanisms of antiperlecan/LG3 antibody production: Importance of T cells and innate B1 cells.
Am J Transplant
; 19(3): 699-712, 2019 03.
Article
en En
| MEDLINE
| ID: mdl-30129231
ABSTRACT
Autoantibodies against perlecan/LG3 (anti-LG3) have been associated with increased risks of delayed graft function, acute rejection, and reduced long-term survival. High titers of anti-LG3 antibodies have been found in de novo renal transplants recipients in the absence of allosensitizing or autoimmune conditions. Here, we seek to understand the pathways controlling anti-LG3 production prior to transplantation. Mice immunized with recombinant LG3 produce concomitantly IgM and IgG anti-LG3 antibodies suggesting a memory response. ELISpot confirmed the presence of LG3-specific memory B cells in nonimmunized mice. Purification of B1 and B2 subtypes identified peritoneal B1 cells as the major source of memory B cells reactive to LG3. Although nonimmunized CD4-deficient mice were found to express LG3-specific memory B cells, depletion of CD4+ T cells in wild type mice during immunization significantly decreased anti-LG3 production. These results demonstrate that B cell memory to LG3 is T cell independent but that production of anti-LG3 antibodies requires T cell help. Further supporting an important role for T cells in controlling anti-LG3 levels, we found that human renal transplant recipients show a significant decrease in anti-LG3 titers upon the initiation of CNI-based immunosuppression. Collectively, these results identify T cell targeting interventions as a means of reducing anti-LG3 levels in renal transplant patients.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Autoanticuerpos
/
Linfocitos B
/
Linfocitos T
/
Proteoglicanos de Heparán Sulfato
/
Funcionamiento Retardado del Injerto
/
Memoria Inmunológica
/
Formación de Anticuerpos
Límite:
Animals
Idioma:
En
Revista:
Am J Transplant
Asunto de la revista:
TRANSPLANTE
Año:
2019
Tipo del documento:
Article
País de afiliación:
Canadá