FcγRIIb expression on B cells is associated with treatment efficacy for acute rejection after kidney transplantation

Mol Immunol. 2017 May:85:283-292. doi: 10.1016/j.molimm.2017.03.006. Epub 2017 Mar 27.

Abstract

Background: Fcγ receptors (FcγR) play a role in the acute rejection (AR) of organ transplants. FcγRIIB is an inhibitory FcγR expressed on B cells. Intravenous IgG (IVIG) and CD28 monoclonal antibody (mAb) have been shown to have immunomodulatory properties against AR.

Aim: To examine the association between FcγRIIB expression on B cell subpopulations and AR treatment efficacy.

Methods: Male F344 rats were used as kidney donors and Lewis rats as recipients to establish models of renal transplantation. Rats were divided into five groups: sham, AR-PBS, AR-IVIG, AR-PNGase F-IVIG, and AR-CD28. Serum creatinine (Scr), blood urea nitrogen (BUN), and urine protein content were determined. Inflammatory markers were measured by ELISA, FcγR by western blotting, and spleen B cell activation by flow cytometry.

Results: Scr, BUN, urinary protein content, levels of CRP, IL-10, TNF-α, IL-6, IL-8, and IgG were all increased in the AR-PBS group compared with the sham group (all P<0.01); these increases were partly reversed in the AR-IVIG, AR-PNGase F IVIG, and AR-CD28 groups (all P<0.01), with IVIG showing the better efficacy than PNGase F IVIG. Furthermore, blood and spleen FcγRIA and FcγRIIIA were increased by AR, while FcγRIIB expressions in splenic activated B cells and regulatory B cells were decreased; these changes were partly alleviated by all three treatments, with IVIG having the better effect than PNGase F IVIG.

Conclusion: We observed an association between B cell FcγRIIB expression and treatment efficacy for AR after kidney transplantation in rats.

Keywords: Acute rejection; CD28; Fcγ receptors; Immunoglobulin G; Renal transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Blotting, Western
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Graft Rejection / immunology*
  • Immunoglobulins, Intravenous / pharmacology
  • Kidney Transplantation*
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Male
  • Random Allocation
  • Rats
  • Rats, Inbred F344
  • Rats, Inbred Lew
  • Receptors, IgG / immunology*

Substances

  • Fcgr2b protein, rat
  • Immunoglobulins, Intravenous
  • Receptors, IgG