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CORRESPONDENCE New nomenclature for Fc receptor–like molecules To the editor: FCRL1 FCRL2 FCRL3 FCRL4 FCRL5 FCRL6 FCRLA FCRLB Newly identified Fc receptor–like genes are referred to in various publications as Fc recep- tor homologs (FcRH)1, immunoglobulin Human superfamily receptor translocation-associated genes (IRTA)2, immunoglobulin-Fc-gp42– related genes (IFGP)3, Src homology 2 domain– containing phosphatase anchor proteins (SPAP) or B cell crosslinked by anti–immuno- globulin M–activating sequences (BXMAS). http://www.nature.com/natureimmunology Prev ious Eight human and six mouse Fc receptor–like symbols : FcRH1 FcRH2 FcRH3 IRTA1 IRTA2 FcRH6 FCRL FcRL2 IRTA5 IRTA4 IRTA3 FcRH4 FcRH5 IFGP6 FREB FREB2 genes have been identified. Correspondence IFGP1 IFGP4 IFGP3 IFGP2 IFGP5 FcRX FcRY organized by the International Committee on BXMAS1 BXMAS2 BXMAS3 BXMAS SPAP1 SPAP2 Standardized Genetic Nomenclature for Mice, Accession the Mouse Genomic Nomenclature Committee number: NM_052938 NM_030764 NM_052939 NM_031282 NM_031281 NM_001004310 NM_032738 NM_001002901 and the Human Genome Organisation Gene Nomenclature Committee has emphasized FCRL1 FCRL5 FCRL6 FCRLS FCRLA FCRLB the need for a unified nomenclature to clas- sify these genes and has proposed the term Mouse ‘Fc receptor–like’ (‘FCRL’ or ‘Fcrl’). Nature Publishing Group Group Nature Publishing The chromosomal position and genomic 6 organization of ‘FCRL’ family is conserved 200 with that of the ‘classical’ Fc receptor (‘FCR’) © gene family. FCRL1–FCRL5 are tandemly located in the 1q21–23 region near FCGR1, Prev ious whereas FCRL6 is located closer to FCER1A. symbols : FcRH1 FcRH3 FcRH6 FcRH2 Fcrl1 Fcrl2 IFGP1 mBXMH2 IFGP2 FREB FREB2 FCRL1–FCRL6 encode type I transmem- BXMAS1 MSR2 FcRX FcRY Accession brane glycoproteins containing three to nine number: NM_153090 NM_183222 Unassigned NM_030707 NM_145141 NM_001029984 extracellular immunoglobulin domains and cytoplasmic immunoreceptor tyrosine-based Figure 1 Human and mouse Fc receptor–like proteins. Colors of immunoglobulin domains indicate activation–like motifs and/or immunoreceptor their phylogenetic relationships. Immunoreceptor tyrosine-based inhibition motifs, red boxes; immunoreceptor tyrosine-based activation–like motifs, green boxes; type B scavenger receptor cysteine- tyrosine-based inhibition motifs (Fig. 1, top). rich domain, gray box; mucin-rich regions, blue triangles. The first domain of FCRLA corresponds to a FCRL1 contains a charged residue in its trans- partial immunoglobulin domain and the full-length isoforms of both FCRLA and FCRLB are intracellular membrane region, but the transmembrane por- proteins. Accession numbers are for GenBank. tions of FCRL2–FCRL6 are hydrophobic and uncharged. FCRL1–FCRL5 are ‘preferentially’ expressed by B cells, whereas FCRL6 is expressed other ‘FCR’ and ‘FCRL’ genes. Both FcRL and FcRH3 are positioned near Fcgr1 on chro- mainly by T cells and natural killer cells. FcRL2 are expressed by B cells as well as non- mosome 3 and encode proteins containing Two additional human ‘FCRL’ genes, origi- lymphoid cells and encode immunoglobulin- two to five immunoglobulin domains with nally called FcRL (also known as FREB or FcRX) like molecules that lack transmembrane regions or without transmembrane regions5 (Fig. 1, and FcRL2 (also known as FREB2 or FcRY)4, and tyrosine-based signaling motifs, but dis- bottom). FcRH1 and FcRH3 are expressed have unusual features that justify their desig- tinctly have C-terminal mucin-like regions. by B cells and encode molecules containing nation as a separate subfamily. These genes are The nomenclature we suggest for these genes is cytoplasmic tyrosine-based signaling motifs. located in the low-affinity ‘FCR’ locus on chro- FCRLA (for FcRL) and FCRLB (for FcRL2). Uniquely, FcRH2 does not cluster with FcRH1 mosome 1q23 and contain two or three immu- The mouse ‘Fcr’ locus is divided between and FcRH3, lacks a human ortholog or lym- noglobulin domains (Fig. 1, top). However, chromosomes 1 and 3. The genes origi- phoid expression and encodes a molecule FcRL lacks exons encoding a split signal pep- nally called FcRH1 (also known as Ifgp1), containing a C-terminal type B scavenger tide, a genomic organization characteristic of FcRH2 (also known as Ifgp2 and Msr2) and receptor cysteine-rich domain without a NATURE IMMUNOLOGY VOLUME 7 NUMBER 5 MAY 2006 431 CORRESPONDENCE transmembrane region. We support the identified. We propose the designation ‘v’ fol- 1Mouse Genome Informatics Resource, MGD assignment of the symbol Fcrl1 for the gene lowed by a number, such as Fcrl1_v1, to des- Nomenclature Group, Jackson Laboratory, previously known as FcRH1 and the symbol ignate splice variants. As cluster designations Bar Harbor, Maine 04609, USA. 2 Fcrl5 for the gene previously known as FcRH3 are assigned, we anticipate modifications of Human Genome Organisation Gene (given its sequence identity and surrounding the nomenclature to accommodate this new Nomenclature Committee, Galton Laboratory, University College London, London NW1 2HE, genomic homology) and propose the symbol extended receptor family. UK. Fcrls for FcRH2 (to emphasize that it has a 3 1. Davis, R.S., Wang, Y.H., Kubagawa, H. & Cooper, M.D. Institute of Cytology and Genetics, Novosibirsk scavenger receptor cysteine-rich motif). Proc. Natl. Acad. Sci. USA 98, 9772–9777 (2001). 630090, Russia. Three additional mouse ‘Fcrl’ genes are 2. Hatzivassiliou, G. et al. Immunity 14, 277–289 4Department of Pathology and Immunology, (2001). located near the low-affinity ‘Fcr’ locus on 3. Guselnikov, S.V. et al. Immunogenetics 54, 87–95 Washington University School of Medicine, mouse chromosome 1. FcRH6, FcRL (also (2002). St. Louis, Missouri 63110, USA. known as Freb and FcRX) and FcRL2 (also 4. Mechetina, L.V. et al. Eur. J. Immunol. 32, 87–96 5Laboratory of Molecular Genetics and (2002). known as Freb2 and FcRY) are located in syn- Immunology, Rockefeller University, New York, 5. Davis, R.S., Stephan, R.P., Chen, C.C., Dennis, G., Jr. & New York 10021, USA. tenic regions relative to their human ortho- Cooper, M.D. Int. Immunol. 16, 1343–1353 (2004). 6Institute for Cancer Genetics, Columbia logs. The new names we suggest for these genes University, New York, New York 10032, USA. are Fcrl6, Fcrla and Fcrlb, respectively. Lois J Maltais1, Ruth C Lovering2, Alexander V 7Division of Developmental and Clinical Expression patterns, functions and ligands Taranin3, Marco Colonna4, Jeffrey V Ravetch5, Immunology, University of Alabama at of Fc receptor-like molecules are being inves- Riccardo Dalla-Favera6, Peter D Burrows7, Birmingham, Birmingham, Alabama 35294, USA. tigated and additional splice isoforms may be Max D Cooper7 & Randall S Davis7 e-mail: [email protected] http://www.nature.com/natureimmunology Nature Publishing Group Group Nature Publishing 6 200 © 432 VOLUME 7 NUMBER 5 MAY 2006 NATURE IMMUNOLOGY.