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* Division of Developmental and Clinical Immunology,
Division of Hematology/Oncology,
Department of Microbiology, and
Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294
Two members of the recently identified FcR homolog (FcRH) family in mice demonstrate preferential B cell expression. One of these, FcRH3, encodes a type I transmembrane protein with five extracellular Ig domains and a cytoplasmic tail with a consensus ITIM and a noncanonical ITAM. Analysis of full-length cDNAs from five different mouse strains defines two FcRH3 alleles. A panel of FcRH3-specific mAbs was generated to define its expression pattern and functional potential on B lineage cells. Although poorly detected on the majority of bone marrow or peripheral blood cells, FcRH3 was readily identified on splenic marginal zone (MZ) and MZ precursor B cells, but not on the bulk of newly formed B cells, follicular B cells, germinal center B cells, and plasma cells. In the peritoneal cavity, FcRH3 was found on B1 cells, and not on the majority of B2 cells. Consistent with its possession of an ITIM and ITAM-like sequence, FcRH3 was tyrosine phosphorylated following pervanadate treatment, and its coligation with the BCR inhibited calcium mobilization. These results suggest FcRH3 is a novel immunoregulatory marker of MZ and B1 B lineage cells.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grants CA13148 and AI14782 (to J.F.K.). R.S.D. was supported in part by National Institutes of Health K08 Award AI55638.
2 Address correspondence and reprint requests to Dr. Randall S. Davis, Division of Developmental and Clinical Immunology, Department of Medicine, University of Alabama at Birmingham, 401 Shelby Biomedical Research Building, 1825 University Boulevard, Birmingham, AL 35294. E-mail address: rsdavis{at}uab.edu
3 Abbreviations used in this paper: PC, plasma cell; MZ, marginal zone; FO, follicular; FcRH3, FcR homolog 3; PNA, peanut lectin agglutinin; HA, hemagglutinin; SRBC, sheep RBC; SA, streptavidin; WT, wild type; IP, immunoprecipitation; GC, germinal center; PEC, peritoneal cavity; BM, bone marrow; SNP, single nucleotide polymorphism.
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