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Blood, 1 April 2005, Vol. 105, No. 7, pp. 2812-2820.
Prepublished online as a Blood First Edition Paper on December 2, 2004; DOI 10.1182/blood-2004-07-2630.


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Submitted July 15, 2004
Accepted November 17, 2004

Tumor protein D52 (TPD52): A novel B-cell/plasma cell molecule with unique expression pattern and Ca2+-dependent association with Annexin VI

Enrico Tiacci, Pier-Luigi Orvietani, Barbara Bigerna, Alessandra Pucciarini, Garry L Corthals, Valentina Pettirossi, Maria P Martelli, Arcangelo Liso, Roberta Benedetti, Roberta Pacini, Niccolo Bolli, Stefano Pileri, Karen Pulford, Marcello Gambacorta, Antonino Carbone, Carla Pasquarello, Alexander Scherl, Helen Robertson, Maria T Sciurpi, Giovanni Alunni-Bistocchi, Luciano Binaglia, Jennifer A Byrne, and Brunangelo Falini*

Institutes of Hematology and Biochemistry, University of Perugia, Perugia, Italy
Geneva Proteomics Research Center, Geneva, Switzerland
Institute of Hematology, University of Foggia, Foggia, Italy
Institute of Pathology, Policlinico S. Orsola, Bologna, Italy
LRF Immunodiagnostic Unit, John Radcliffe Hospital, Oxford, United Kingdom
Institute of Pathology, Niguarda Hospital, Milan, Italy
Division of Pathology, Oncology Reference Center, National Tumor Institute, Aviano, Italy
Oncology Research Unit and the University of Sydney Department of Pediatrics and Child's Health, The Children's Hospital at Westmead, Westmead, NSW, Australia

* Corresponding author; email: faliniem{at}unipg.it.

We generated a murine monoclonal antibody (B28p) detecting an antigenic determinat shared by the IRTA1 receptor (the immunogen used to raise B28p) and an unrelated 28 kDa protein that was subsequently subjected to extensive characterization. The expression of the 28 kDa protein in normal lympho-hemopoietic tissues was restricted to B-cells and plasma cells, and clearly differed from that expected for IRTA1 (selectively expressed by MALT marginal zone B-cells). 2D-PAGE/mass-spectrometry analysis identified the 28 kDa protein as human TPD52, whose expression had been previously described only in normal and neoplastic epithelia. Specific B28p reactivity with TPD52 was confirmed by immunostaining/immunoblotting of TPD52-transfected cells. TPD52 expression pattern in normal and neoplastic B-cells was unique. In fact, unlike other B-cell molecules (PAX5, CD19, CD79a, CD20, CD22), which are down-regulated during differentiation from B cells to plasma cells, TPD52 expression reached its maximum levels at the plasma cell stage. In the Thiel myeloma cell line, TPD52 bound to annexin VI in a Ca+2-dependent manner, suggesting that these molecules, similarly to what observed in pancreatic acinar cells, may act in concert to regulate secretory processes in plasma cells. Finally, the anti-TPD52 monoclonal antibody served as a valuable tool for the diagnosis of B-cell malignancies.


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