Suppression of FVIII-specific Memory B Cells by Regulatory T Cells Expressing BARs
ISTH Academy. Zhang A. Jul 10, 2019; 274138; OC 76.2 Topic: Coagulation Factors & Inhibitors
Ai-Hong Zhang
Ai-Hong Zhang
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OC 76.2

Suppression of FVIII-specific Memory B Cells by Regulatory T Cells Expressing BARs

A.-H. Zhang, S.H. Venkatesha, D.W. Scott
Uniformed Services University of the Health Sciences, Bethesda, United States

Main Topic: Coagulation and Anticoagulation
Category: Coagulation Factors & Inhibitors

Background: Anti-FVIII neutralizing antibody (inhibitor) formation poses significant obstacles for optimal treatment of hemophilia A. We have recently shown that human regulatory T cells (Tregs) expressing a FVIII-domain as a chimeric B-cell antibody receptor (BAR) prevented anti-FVIII antibody formation in hemophilic mice by directly suppressing B cells (Zhang AH, J Immunol. 201:1434-1441, 2018).
Aims: In this study, we sought to determine whether FVIII-specific memory B cells could be suppressed by the FVIII BAR Tregs.
Methods: To test this in vitro, we used plasmablast-depleted splenocytes from FVIII immunized hemophilia mice to serve as the source of FVIII-specific memory B cells.
Results: Co-culture of CD138- splenocytes with FVIII antigen in the presence of FVIII A2-domain BAR human Tregs completely blocked the development of FVIII-specific antibody forming cells (ASC). In addition, FVIII A2-BAR human Tregs efficiently suppressed FVIII-specific ASC formation in the presence of anti-FVIII antibodies in vitro. Similar results were obtained when BAR-expressing murine Tregs were used.
Conclusions: In conclusion, we demonstrated in vitro that FVIII BAR Tregs suppress FVIII-specific memory B cells activity. The efficacy of FVIII BAR Tregs on FVIII-specific memory B cells will be further tested in vivo by adoptive transfer of FVIII-specific memory B cells in syngeneic hosts. Supported by a Bayer Hemophilia Grant [AHZ] and NIH HL126727 [DWS].

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