Inducing cell-intrinsic dysfunction in pregnancy-sensitized alloreactive B cells

نویسندگان

چکیده

Abstract Objective: Pregnancy is an immunological paradox where the maternal immune system develops tolerance to semi-allogeneic fetus yet a sensitizing event that detrimental subsequent organ transplantation. Humoral sensitization by pregnancy in WT mice prevents anti-CD154-mediated matched allograft. In contrast, lacking secreted immunoglobulins (mIgM −/−AID −/−; SIgKO) permitted anti-CD154 mediated transplant tolerance, suggesting fetus-specific antibodies (FSA) were mediating resistance anti-CD154. Here, we tested whether pregnancy-induced memory B cells could be desensitized acquire state of cell-intrinsic dysfunction. Methods: Pregnancy-sensitized SIgKO or subjected fetus-matched heart transplant/anti-CD154 (PP-tolerant B) not (PP-memory B). Enriched adoptively transferred (AdTr) into secondary hosts (MD4 mice) and challenged with splenocytes. Germinal center (GC) allo-reactive from MD4 identified MHC tetramers, Fas +GL7 +. Results: While PP-memory differentiated GC-B hosts; this was significantly decreased 7–10-fold PP-tolerant cells. comparably Conclusions: absence FSA, PP can hypo-functional state. This suggests possible cell desensitization for multiparous women, who are currently disadvantaged humoral sensitization. R01AI42747, P01AI097113

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ژورنال

عنوان ژورنال: Journal of Immunology

سال: 2023

ISSN: ['1550-6606', '0022-1767']

DOI: https://doi.org/10.4049/jimmunol.210.supp.173.37