Impact Factor 4.716 | CiteScore 4.71
More on impact ›

Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02061

The complex association of FcγRIIb with autoimmune susceptibility

 Joseph S. Verbeek1*, Sachiko Hirose1 and Hiroyuki Nishimura1
  • 1Toin University of Yokohama, Japan

The complex association of FcγRIIb with autoimmune susceptibility

Abstract

FcγRIIb is the only inhibitory Fc receptor and controls many aspects of immune and inflammatory responses. The observation 18 years ago that FcγRIIb-/- mice generated by gene targeting in 129 derived ES cells developed severe lupus like disease when backcrossed more than 7 generations into C57BL/6 background initiated extensive research on the genetic basis and functional understanding of this strong autoimmune phenotype. The genomic region in the distal part of Chr1 both in human and mice in which the FcγR gene is located shows a high level of complexity in relation to the susceptibility to SLE. Specific haplotypes of closely linked genes including the FcγRIIb and SLAMF genes are associated with increased susceptibility to SLE both in mice and human. Using forward and reverse genetic approaches including in human GWAS and in mice congenic strains, KO mice, (germline and cell type specific, on different genetic background), knockin mice, overexpressing transgenic mice combined with immunological models such as adoptive transfer of B cells from Ig transgenic mice the genes involved and the causing mutations and their functional alterations were analyzed. In this review the results of this 18 years extensive research are discussed with a focus on (genetically modified) mouse models.

Keywords: SLE, systemic lupus erythematosus, Autoimmue Disease, mouse model, Fcgamma receptor IIB, Reverse Genetics

Received: 06 Jan 2019; Accepted: 15 Aug 2019.

Copyright: © 2019 Verbeek, Hirose and Nishimura. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Joseph S. Verbeek, Toin University of Yokohama, Yokohama, Japan, j.s.verbeek@toin.ac.jp