title: MS4A4A: a novel cell surface marker for M2 macrophages and plasma cells.
abstract: MS4A4A is a member of the membrane-spanning, four domain family, subfamily A (MS4A) that includes CD20 (MS4A1), FcRβ (MS4A2) and Htm4 (MS4A3). Like the first three members of this family, transcription of MS4A4A appears to be limited to hematopoietic cells. To evaluate expression of the MS4A4A protein in hematopoietic cell lineages and subsets we generated monoclonal antibodies against extracellular epitopes for use in flow cytometry. In human peripheral blood we found that MS4A4A is expressed at the plasma membrane in monocytes but not in granulocytes or lymphocytes. In vitro differentiation of monocytes demonstrated that MS4A4A is expressed in immature but not activated dendritic cells, and in macrophages generated in the presence of interleukin-4 ('alternatively activated' or M2 macrophages) but not by interferon-γ and lipopolysaccharide ('classically' activated or M1 macrophages). MS4A4A was expressed in the U937 monocytic cell line only after differentiation. In normal bone marrow, MS4A4A was expressed in mature monocytes but was undetected, or detected at only a low level, in myeloid/monocytic precursors, as well as their malignant counterparts in patients with various subtypes of myeloid leukemia. Although MS4A4A was not expressed in healthy B lymphocytes, it was highly expressed in normal plasma cells, CD138+ cells from multiple myeloma patients, and bone marrow B cells from a patient with mantle cell lymphoma. These findings suggest immunotherapeutic potential for MS4A4A antibodies in targeting alternatively activated macrophages such as tumor-associated macrophages, and in the treatment of multiple myeloma and mantle cell lymphoma.
authors.affiliation: Department of Biochemistry and Molecular Biology, and Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Ratna
authors.initials: R
authors.lastname: Sanyal
authors.affiliation: Department of Biochemistry and Molecular Biology, and Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Polyak
authors.affiliation: Department of Biochemistry and Molecular Biology, and Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Zuccolo
authors.affiliation: Department of Biochemistry and Molecular Biology, and Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Mandip
authors.initials: M
authors.lastname: Puri
authors.affiliation: Department of Biochemistry and Molecular Biology, and Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Lili
authors.initials: L
authors.lastname: Deng
authors.affiliation: Department of Biochemistry and Molecular Biology, and Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Luc
authors.initials: L
authors.lastname: Roberts
authors.affiliation: Department of Biochemistry and Molecular Biology, and Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Ania
authors.initials: A
authors.lastname: Zuba
authors.affiliation: Departments of Medicine and Oncology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Jan
authors.initials: J
authors.lastname: Storek
authors.affiliation: Calgary Laboratory Services, Foothills Medical Centre, Calgary, Alberta, Canada.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Luider
authors.affiliation: Calgary Laboratory Services, Foothills Medical Centre, Calgary, Alberta, Canada.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Sundberg
authors.affiliation: Calgary Laboratory Services, Foothills Medical Centre, Calgary, Alberta, Canada.|Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Adnan
authors.initials: A
authors.lastname: Mansoor
authors.affiliation: Department of Oncology, University of Alberta and Cross Cancer Institute, Edmonton, Alberta, Canada.
authors.forename: Eva
authors.initials: E
authors.lastname: Baigorri
authors.affiliation: Department of Oncology, University of Alberta and Cross Cancer Institute, Edmonton, Alberta, Canada.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Chu
authors.affiliation: Department of Oncology, University of Alberta and Cross Cancer Institute, Edmonton, Alberta, Canada.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Belch
authors.affiliation: Department of Oncology, University of Alberta and Cross Cancer Institute, Edmonton, Alberta, Canada.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Pilarski
authors.affiliation: Department of Biochemistry and Molecular Biology, and Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Julie P
authors.initials: JP
authors.lastname: Deans
mesh_terms: D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001773:Blood Cells / Q000187:drug effects / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007951:Leukemia, Myeloid / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins / Q000097:blood / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010950:Plasma Cells / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D020298:U937 Cells; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D015415:Biomarkers; C424714:MS4A4A protein, human; D008565:Membrane Proteins; D016179:Granulocyte Colony-Stimulating Factor; D013755:Tetradecanoylphorbol Acetate