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CD72 is an inhibitory pattern recognition receptor that recognizes ribosomes and suppresses production of anti-ribosome autoantibody.
- 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.)
- Subjects :
- Animals
Mice
Mice, Knockout
Lymphocyte Activation immunology
Cell Proliferation
Immune Tolerance
Humans
Ribosomes metabolism
Ribosomes immunology
Receptors, Antigen, B-Cell metabolism
Receptors, Antigen, B-Cell immunology
Autoantibodies immunology
Lupus Erythematosus, Systemic immunology
Lupus Erythematosus, Systemic metabolism
Antigens, Differentiation, B-Lymphocyte immunology
Antigens, Differentiation, B-Lymphocyte metabolism
Antigens, CD metabolism
Antigens, CD immunology
B-Lymphocytes immunology
B-Lymphocytes metabolism
Signal Transduction immunology
Autoantigens immunology
Subjects
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