New insights into immune mechanisms of antiperlecan/LG3 antibody production: Importance of T cells and innate B1 cells.

Autor: Padet L; Research Centre, Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada.; Canadian National Transplant Research Program, Edmonton, Alberta, Canada.; Université de Montréal, Montreal, Quebec, Canada., Dieudé M; Research Centre, Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada.; Canadian National Transplant Research Program, Edmonton, Alberta, Canada., Karakeussian-Rimbaud A; Research Centre, Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada.; Canadian National Transplant Research Program, Edmonton, Alberta, Canada., Yang B; Research Centre, Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada.; Canadian National Transplant Research Program, Edmonton, Alberta, Canada.; Université de Montréal, Montreal, Quebec, Canada., Turgeon J; Research Centre, Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada.; Canadian National Transplant Research Program, Edmonton, Alberta, Canada., Cailhier JF; Research Centre, Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada.; Canadian National Transplant Research Program, Edmonton, Alberta, Canada., Cardinal H; Research Centre, Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada.; Canadian National Transplant Research Program, Edmonton, Alberta, Canada., Hébert MJ; Research Centre, Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada.; Canadian National Transplant Research Program, Edmonton, Alberta, Canada.; Université de Montréal, Montreal, Quebec, Canada.
Jazyk: angličtina
Zdroj: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2019 Mar; Vol. 19 (3), pp. 699-712. Date of Electronic Publication: 2018 Sep 17.
DOI: 10.1111/ajt.15082
Abstrakt: 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.
(© 2018 The Authors American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)
Databáze: MEDLINE
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