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Regulatory B Cell‐Dependent Islet Transplant Tolerance Is Also Natural Killer Cell Dependent
Author(s) -
Schuetz C.,
Lee K. M.,
Scott R.,
Kojima L.,
Washburn L.,
Liu L.,
Liu W.H.,
Tector H.,
Lei J.,
Yeh H.,
Kim J. I.,
Markmann J. F.
Publication year - 2017
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.14265
Subject(s) - regulatory b cells , natural killer t cell , immune tolerance , islet , cd1d , immunology , transplantation , biology , antibody , microbiology and biotechnology , natural killer cell , immune system , b cell , medicine , cytotoxic t cell , t cell , endocrinology , insulin , biochemistry , in vitro
Immunologic tolerance to solid organ and islet cell grafts has been achieved in various rodent models by using antibodies directed at CD 45 RB and Tim‐1. We have shown that this form of tolerance depends on regulatory B cells (Bregs). To elucidate further the mechanism by which Bregs induce tolerance, we investigated the requirement of natural killer ( NK ) and NKT cells in this model. To do so, hyperglycemic B6, μ MT , Beige, or CD 1d − / − mice received BALB/c islet grafts and treatment with the tolerance‐inducing regimen consisting of anti‐ CD 45 RB and anti‐ TIM 1. B6 mice depleted of both NK and NKT cells by anti‐ NK 1.1 antibody and mice deficient in NK activity (Beige) did not develop tolerance after dual‐antibody treatment. In contrast, transplant tolerance induction was successful in CD 1d − / − recipients (deficient in NKT cells), indicating that NK , but not NKT , cells are essential in B cell–dependent tolerance. In addition, reconstitution of Beige host with NK cells restored the ability to induce transplant tolerance with dual‐antibody treatment. Transfer of tolerance by B cells from tolerant mice was also dependent on host Nk1.1 + cells. In conclusion, these results show that regulatory function of B cells is dependent on NK cells in this model of transplantation tolerance.