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

Chizuru Akatsu; Takahiro Tsuneshige; Nobutaka Numoto; Wang Long; Toshio Uchiumi; Yoshikatsu Kaneko; Masatake Asano; Nobutoshi Ito; Takeshi Tsubata

doi:10.1016/j.jaut.2024.103245

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

J Autoimmun. 2024 May 15:146:103245. doi: 10.1016/j.jaut.2024.103245. Online ahead of print.

Authors

Chizuru Akatsu¹, Takahiro Tsuneshige², Nobutaka Numoto³, Wang Long⁴, Toshio Uchiumi⁵, Yoshikatsu Kaneko⁶, Masatake Asano⁴, Nobutoshi Ito³, Takeshi Tsubata⁷

Affiliations

¹ Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
² Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan; Nihon University School of Dentistry, Tokyo, Japan.
³ Department of Structural Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
⁴ Nihon University School of Dentistry, Tokyo, Japan.
⁵ Department of Biology, Niigata University School of Science, Niigata, Japan.
⁶ Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
⁷ Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan; Nihon University School of Dentistry, Tokyo, Japan. Electronic address: tsubata.imm@mri.tmd.ac.jp.

PMID: 38754236
DOI: 10.1016/j.jaut.2024.103245

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^-/- but not CD72^+/+ 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.

Keywords: Anti-ribosome antibody; B cell; CD72; RNA sensor; SLE; Self-tolerance.