Reversing Endogenous Alloreactive B Cell GC Responses With Anti‐CD154 or CTLA‐4Ig. Issue 9 (15th July 2013)

• Record Type: Journal Article
• Authors: Chen, J.; Yin, H.; Xu, J.; Wang, Q.; Edelblum, K. L.; Sciammas, R.; Chong, A. S.
• Is Part Of: American journal of transplantation. Volume 13:Issue 9(2013)
• Page Start: 2280
• Page End: 2292
• Publication Date: 2013-07-15
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.12350
• Languages: English
• ISSNs: 1600-6135

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="ajt12350-sec-0001" sec-type="section"> <p>Alloantibodies mediate acute antibody‐mediated rejection as well as chronic allograft rejection in clinical transplantation. To better understand the cellular dynamics driving antibody production, we focused on the activation and differentiation of alloreactive B cells in the draining lymph nodes and spleen following sensitization to allogeneic cells or hearts. We used a modified staining approach with a single MHC Class I tetramer (K<sup>d</sup>) bound to two different fluorochromes to discriminate between the Class I‐binding and fluorochrome‐streptavidin‐binding B cells with a high degree of specificity and binding efficiency. By Day 7–8 postsensitization, there was a 1.5‐ to 3.2‐fold increase in the total numbers of K<sup>d</sup>‐binding B cells. Within this K<sup>d</sup>‐binding B cell population, approximately half were IgD<sup>low</sup>, MHC Class II<sup>high</sup> and CD86<sup>+</sup>, 30–45% expressed a germinal center (Fas<sup>+</sup>GL7<sup>+</sup>) phenotype and 3–12% were IRF4<sup>hi</sup> plasma cells. Remarkably, blockade with anti‐CD40 or CTLA‐4Ig, starting on Day 7 postimmunization for 1 or 4 weeks, completely dissolved established GCs and halted further development of the alloantibody response. Thus MHC Class I tetramers can specifically track the <italic>in vivo</italic> fate of endogenous, Class I‐specific B cells and was used to demonstrate the ability of delayed treatment with anti‐CD154 or CTLA‐4Ig to halt established allo‐B cell responses.</p> </sec> </abstract>