Rabbit Anti-Human MS4A3 (a.a. 51-150) Polyclonal antibody

MS4A4A is a member of the membrane-spanning, four domain family, subfamily A (MS4A) that includes CD20 (MS4A1), FcR beta (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-gamma 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.

Proteins with transmembrane domains are classified in different families based on their structure, amino acid homology, and function. In this. study, we report the identification, sequence, and expression profile of a new member of the CD20/Fc epsilon RI beta family, CD20/Fc epsilon RI beta family member 4 (CFFM4). The CFFM4 gene contains seven exons and six introns and is transcribed into an mRNA encoding a 240-amino acid protein with four hydrophobic regions. The CFFM4 protein shares a high degree of, homology with the other members of the family, especially in the hydrophobic regions where several amino acids are conserved. However, the CFFM4 protein can be distinguished from the other members of the family based on the length of the second extracellular loop and the absence. of an immunoreceptor tyrosine-based activation motif signal. Another distinct characteristic is that CFFM4 mRNA expression is not limited to the hematopoietic lineage. CFFM4 was detected by Northern dot blot in a variety of normal and cancerous tissues. CFFM4 expression was also compared in developmentally early hematopoietic human bone marrow CD34+ stem cells versus peripheral blood-derived CD14+ mature monocytes, in the undifferentiated versus differentiated myelomonocytic U937 cell line, and in acute myelogenous leukemia FAB1 versus FAB5. In each of these systems,cellular myelomonocytic differentiation correlated with an increase in CFFM4 mRNA expression. Such results indicate that CFFM4 is associated with mature cellular function in the monocytic lineage and like CD20 and Fc epsilon RI beta, it may be a component of a receptor complex involved in signal transduction.