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CD72 is an inhibitory pattern recognition receptor that recognizes ribosomes and suppresses production of anti-ribosome autoantibody.

Authors :
Akatsu C
Tsuneshige T
Numoto N
Long W
Uchiumi T
Kaneko Y
Asano M
Ito N
Tsubata T
Source :
Journal of autoimmunity [J Autoimmun] 2024 Jun; Vol. 146, pp. 103245. Date of Electronic Publication: 2024 May 15.
Publication Year :
2024

Abstract

B cell responses to nucleic acid-containing self-antigens that involve intracellular nucleic acid sensors play a crucial role in autoantibody production in SLE. CD72 is an inhibitory B cell co-receptor that down-regulates BCR signaling, and prevents the development of SLE. We previously showed that CD72 recognizes the RNA-containing self-antigen Sm/RNP, a target of SLE-specific autoantibodies, and induces B cell tolerance to Sm/RNP by specifically inhibiting B cell response to this self-antigen. Here, we address whether CD72 inhibits B cell response to ribosomes because the ribosome is an RNA-containing self-antigen and is a target of SLE-specific autoantibodies as well as Sm/RNP. We demonstrate that CD72 recognizes ribosomes as a ligand, and specifically inhibits BCR signaling induced by ribosomes. Although conventional protein antigens by themselves do not induce proliferation of specific B cells, ribosomes induce proliferation of B cells reactive to ribosomes in a manner dependent on RNA. This proliferative response is down-regulated by CD72. These results suggest that ribosomes activate B cells by inducing dual signaling through BCR and intracellular RNA sensors and that CD72 inhibits B cell response to ribosomes. Moreover, CD72 <superscript>-/-</superscript> but not CD72 <superscript>+/+</superscript> mice spontaneously produce anti-ribosome autoantibodies. Taken together, CD72 induces B cell self-tolerance to ribosomes by recognizing ribosomes and inhibiting RNA-dependent B cell response to this self-antigen. CD72 appears to prevent development of SLE by inhibiting autoimmune B cell responses to multiple RNA-containing self-antigens. Because these self-antigens but not protein self-antigens induce RNA-dependent B cell activation, self-tolerance to RNA-containing self-antigens may require a distinct tolerance mechanism mediated by CD72.<br />Competing Interests: Declaration of competing interest The authors declare no conflicts of interests.<br /> (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Details

Language :
English
ISSN :
1095-9157
Volume :
146
Database :
MEDLINE
Journal :
Journal of autoimmunity
Publication Type :
Academic Journal
Accession number :
38754236
Full Text :
https://doi.org/10.1016/j.jaut.2024.103245