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Inhibitory Receptors and Pathways of Lymphocytes

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Front. Immunol. | doi: 10.3389/fimmu.2018.02276

Ligand recognition determines the role of inhibitory B cell co-receptors in the regulation of B cell homeostasis and autoimmunity

  • 1Tokyo Medical and Dental University, Japan

B cells express various inhibitory co-receptors including CD22, CD72 and Siglec-G. These receptors contain immunoreceptor tyrosine-based inhibition motifs (ITIMs) in the cytoplasmic region. Although many of the inhibitory co-receptors negatively regulating BCR signaling by activating SH2-containing protein tyrosine phosphatase 1 (SHP-1), different inhibitory co-receptors have distinct functional properties. CD22, Siglec-G and CD72 preferentially regulate tonic signaling in conventional B cells, B-1 cell homeostasis, and development of lupus-like disease, respectively. CD72 recognizes RNA-related lupus self-antigen Sm/RNP as a ligand. This ligand recognition recruits CD72 to BCR in Sm/RNP-reactive B cells thereby suppressing production of anti-Sm/RNP autoantibody involved in the pathogenesis of lupus. In contrast, Siglec-G recognizes 2,3 as well as 2,6 sialic acids whereas CD22 recognizes 2,6 sialic acid alone. Because glycoproteins including BCR are dominantly glycosylated with 2,3 sialic acids in B-1 cells, Siglec-G but not CD22 recruits BCR as a ligand specifically in B-1 cells, and regulates B-1 cell homeostasis by suppressing BCR signaling in B-1 cells. Thus, recognition of distinct ligands determines functional properties of different inhibitory B cell co-receptors.

Keywords: inhibitory B cell co-receptor, CD72, CD22, Siglec-G, B-1 cells, Systemic lupus erythematosas (SLE), Sm/RNP, sialic acid

Received: 02 Jul 2018; Accepted: 13 Sep 2018.

Edited by:

Aaron J. Marshall, University of Manitoba, Canada

Reviewed by:

Pablo Engel, University of Barcelona, Spain
Louis Justement, University of Alabama at Birmingham, United States  

Copyright: © 2018 Tsubata. 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. Takeshi Tsubata, Tokyo Medical and Dental University, Bunkyō, Japan, tsubata.imm@mri.tmd.ac.jp