Fcmr, also known as Toso, is the putative receptor for soluble IgM. It plays a role in immune regulation, especially in the modulation of myeloid cell responses related to anti-tumor immunity, and is involved in B cell development and homeostasis [1,3]. It may also be associated with pathways related to autoimmunity and response to pathogens [2,4]. Genetic models, such as gene knockout mouse models, have been crucial in studying its functions.

In a syngeneic melanoma model, Fcmr ablation in myeloid cells suppressed tumor growth, extended mouse survival, increased myeloid cell population density, and enhanced anti-tumor immunity. Single-cell RNA sequencing of Fcmr-deficient tumor-associated mononuclear phagocytes revealed a unique subset with enhanced antigen processing/presenting properties. Conversely, Fcmr activity negatively regulated the activation and migratory capacity of myeloid cells in vivo and T cell activation by bone marrow-derived dendritic cells in vitro. Therapeutic targeting of Fcmr during oncogenesis decreased tumor growth when used alone or in combination with anti-PD-1 [1]. In Fcmr-deficient mice, there are reduced numbers of developing B cells, splenic follicular and peritoneal B-2 cells, but increased levels of peritoneal B-1a cells and autoantibodies. After immunization, germinal center B cell and plasma cell numbers are increased, and Fcmr-deficient B cells are sensitive to apoptosis induced by BCR ligation [3].

In conclusion, Fcmr is essential for regulating myeloid cell activation within the tumor microenvironment, and for B cell differentiation and homeostasis. Gene knockout mouse models have demonstrated its significance in anti-tumor immunity and autoimmunity-related processes, providing potential therapeutic targets for cancer and insights into autoimmune disease mechanisms.

References:

1. Kubli, Shawn P, Vornholz, Larsen, Duncan, Gordon, Bray, Mark R, Mak, Tak W. 2019. Fcmr regulates mononuclear phagocyte control of anti-tumor immunity. In Nature communications, 10, 2678. doi:10.1038/s41467-019-10619-w. https://pubmed.ncbi.nlm.nih.gov/31213601/

2. Wang, Hongsheng, Coligan, John E, Morse, Herbert C. 2016. Emerging Functions of Natural IgM and Its Fc Receptor FCMR in Immune Homeostasis. In Frontiers in immunology, 7, 99. doi:10.3389/fimmu.2016.00099. https://pubmed.ncbi.nlm.nih.gov/27014278/

3. Choi, Seung-Chul, Wang, Hongsheng, Tian, Linjie, Morse, Herbert C, Coligan, John E. 2012. Mouse IgM Fc receptor, FCMR, promotes B cell development and modulates antigen-driven immune responses. In Journal of immunology (Baltimore, Md. : 1950), 190, 987-96. doi:10.4049/jimmunol.1202227. https://pubmed.ncbi.nlm.nih.gov/23267023/

4. Kubagawa, Hiromi, Mahmoudi Aliabadi, Pedram, Al-Qaisi, Khlowd, Radbruch, Andreas, Melchers, Fritz. 2024. Functions of IgM fc receptor (FcµR) related to autoimmunity. In Autoimmunity, 57, 2323563. doi:10.1080/08916934.2024.2323563. https://pubmed.ncbi.nlm.nih.gov/38465789/