is preferentially expressed on B cell, and is along the FCRL6 the only gene from this family which is expressed also outside B-cell lineage, as it has been detected also on NK cell and T cell subsets. The rest of the Fc receptor-like family are considered B cell markers. It is expressed in relatively low levels on naïve B cells, germinal center B cells, memory B cells, marginal zone B cells and peripheral blood and tonsil B-cells, and at slightly higher levels on splenic naïve and memory B cells. Its expression was not detected on pro-B cells, pre-B cells and bone marrow-derived plasmatic B cells. Highest levels of FCRL3 expression were detected on circulating memory B cells, as well as innate-like marginal zone B cells. Memory B cell subsets with innate-like properties have also been observed to have higher FCRL3 expression, which had a potent co-stimmulatory effect on TLR9-mediated B cell activation, as well as activation and inhibitory effect on plasma cell differentiation. Outside B cell lineage, FCLR3 expression has been detected on CD56+ natural killer cells, CD4+ and CD8+ T cells, as well as regulatory CD4+FOXP3+ T cells. Notably, it has also been observed on a subpopulation of natural Treg (nTreg) cells with high expression levels of PD-1, which had impaired IL-2 responsiveness, and also on Helios Treg cells, where it was co-expressed with T-cell immunoreceptor with Ig and ITIM domains (TIGIT). Function Given its dual-signalling properties, FCRL3 mediates BCR signalling as well as plasma B cell maturation and antibody production. FCRL3 has been shown to interact with PTPN6. Potential role in disease The FCRL3 loci is associated with numerous autoimmune diseases. Single-nucleotide polymorphism (SNP) -169 C/T located in promoter region of FCRL3 has been linked to higher susceptibility to diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and autoimmune thyroid disease. This polymorphism enhanced expression levels of FCRL3 via more efficient NFκB binding and increased promoted activity. Elevated expression levels of FCRL3 on Treg cells, cytotoxic CD8+ T cells and γδ-T cells are associated with rheumatoid arthritis. FCRL3 gene polymorphism is also associated with multiple sclerosis, autoimmune pancreatitis, type I diabetes and Bahcet’s disease in various populations. Thymus derived FCRL3+ Treg were observed to have higher PD-1 expression and lower responsiveness to antigenic stimulation, as well as reduced suppression properties on effector T cell proliferation. FCRL3 expression on Treg cells is also associated with -169 C/T SNP