CD72, a regulatory co-receptor, is a member of the C-type lectin superfamily. It is expressed on B cells from pro-B to mature B-cell stages and plays a role in regulating lymphocyte responsiveness. Its cytoplasmic tail contains immunoreceptor tyrosine-based inhibitory motifs (ITIMs), suggesting a negative regulatory function, and it is involved in pathways related to immune responses and autoimmunity [1,2,4].

In mouse models, CD72-deficient mice demonstrate that CD72 is a non-redundant regulator of B-cell development and a negative regulator of B-cell responsiveness [2]. In the context of systemic lupus erythematosus (SLE), CD72 polymorphisms associate with SLE in both human and mice, and CD72-/-mice develop relatively severe lupus-like disease. CD72 specifically recognizes self-antigens like Sm/RNP and ribosomes, inhibiting B-cell responses to these self-antigens and thus suppressing the development of SLE [1,3]. In a murine scleroderma model, CD72-deficient mice showed less skin and lung fibrosis compared to wild-type mice, indicating its role in fibrosis development [5].

In summary, CD72 is a crucial regulator in B-cell function, playing a key role in maintaining self-tolerance and preventing autoimmunity. Gene knockout mouse models, such as CD72-/-mice, have been instrumental in revealing its functions in diseases like SLE and scleroderma, providing insights into potential therapeutic targets for these autoimmune diseases.

References:

1. Tsubata, Takeshi. 2019. CD72 is a Negative Regulator of B Cell Responses to Nuclear Lupus Self-antigens and Development of Systemic Lupus Erythematosus. In Immune network, 19, e1. doi:10.4110/in.2019.19.e1. https://pubmed.ncbi.nlm.nih.gov/30838156/

2. Parnes, J R, Pan, C. . CD72, a negative regulator of B-cell responsiveness. In Immunological reviews, 176, 75-85. doi:. https://pubmed.ncbi.nlm.nih.gov/11043769/

3. Akatsu, Chizuru, Tsuneshige, Takahiro, Numoto, Nobutaka, Ito, Nobutoshi, Tsubata, Takeshi. 2024. CD72 is an inhibitory pattern recognition receptor that recognizes ribosomes and suppresses production of anti-ribosome autoantibody. In Journal of autoimmunity, 146, 103245. doi:10.1016/j.jaut.2024.103245. https://pubmed.ncbi.nlm.nih.gov/38754236/

4. Wu, Hsin-Jung, Bondada, Subbarao. . Positive and negative roles of CD72 in B cell function. In Immunologic research, 25, 155-66. doi:. https://pubmed.ncbi.nlm.nih.gov/11999169/

5. Zhao, Chunyan, Matsushita, Takashi, Ha Nguyen, Vinh Thi, Takehara, Kazuhiko, Hamaguchi, Yasuhito. 2019. CD22 and CD72 contribute to the development of scleroderma in a murine model. In Journal of dermatological science, 97, 66-76. doi:10.1016/j.jdermsci.2019.12.007. https://pubmed.ncbi.nlm.nih.gov/31883832/