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Donor-Specificb Cell Dysfunction and Suppressive Ability Are Differentially Induced in Cob-Mediated Transplantation Tolerance

S. Durgam1, D. Yin1, M. Alegre2, A. Chong1

1Surgery, section of transplant immunology, University of Chicago, Chicago, IL, 2Medicine, section of rheumatology, University of Chicago, Chicago, IL

Meeting: 2022 American Transplant Congress

Abstract number: 1248

Keywords: Alloantibodies, B cells, Co-stimulation, Tolerance

Topic: Basic Science » Basic Science » 10 - Treg/Other Regulatory Cell/Tolerance

Session Information

Session Name: Treg/Other Regulatory Cell/Tolerance

Session Type: Poster Abstract

Date: Monday, June 6, 2022

Session Time: 7:00pm-8:00pm

 Presentation Time: 7:00pm-8:00pm

Location: Hynes Halls C & D

*Purpose: B cells in mice tolerized to fully mismatched heart allografts with anti-CD154+donor spleen cells (CoB) are intrinsically dysfunctional and unable to differentiate into germinal center B cells (GCBC) and antibody-secreting cells (ASCs). Remarkably, these B cells acquire the ability to suppress naïve B cell responses in a donor-specific manner. Here we tested whether dysfunction and ability to suppress are induced simultaneously, and due to the lack of sustained T:B interaction that is mediated by SLAM-associated protein (SAP) or absent CD40:CD154 interactions.

*Methods: SAP-KO and CD154-KO B/6 mice were transplanted with B/c hearts without CoB, and on post-operative day 30, enriched B cells were adoptively transferred (AdTr) to secondary MD4 BCR-Tg hosts, either alone or at a 1:1 ratio with naïve B cells, then challenged with B/c spleen cells to test for dysfunction and ability to suppress. Donor-specific IgG from MD4 hosts was quantified on day 14 post-AdTr.

*Results: A) In SAP-KO recipients, donor-specific IgG response was significantly reduced; following AdTr and B/c challenge, SAP-KO B cells were neither dysfunctional nor suppressive. B) In CD154-KO recipients, donor-specific IgG response was completely inhibited; following AdTr and B/c challenge, CD154-KO B cells were intrinsically dysfunctional but failed to suppress naïve B responses. In contrast, AdTr B cells from tolerant WT recipients of B/c hearts and CoB were dysfunctional and suppressed naïve B cell responses.

*Conclusions: B cell dysfunction and ability to suppress are independently induced; dysfunction was induced by the absence of CD40:CD154 interactions, but the ability to suppress was not induced even when CoB was administered to CD154-KO recipients. We are currently testing the hypothesis that low levels of CD40 signaling, as a result of incomplete blockade of CD40:CD154 interactions with CoB, is necessary to induce suppressive properties in donor-specific B cells in tolerant recipients.

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To cite this abstract in AMA style:

Durgam S, Yin D, Alegre M, Chong A. Donor-Specificb Cell Dysfunction and Suppressive Ability Are Differentially Induced in Cob-Mediated Transplantation Tolerance [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/donor-specificb-cell-dysfunction-and-suppressive-ability-are-differentially-induced-in-cob-mediated-transplantation-tolerance/. Accessed May 28, 2025.

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