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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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IMMUNOBIOLOGY

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, Niccolò Bolli, Stefano Pileri, Karen Pulford, Marcello Gambacorta, Antonino Carbone, Carla Pasquarello, Alexander Scherl, Helen Robertson, Maria Teresa Sciurpi, Giovanni Alunni-Bistocchi, Luciano Binaglia, Jennifer A. Byrne, and Brunangelo Falini

From the Section of Physiopathology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy; Geneva Proteomics Research Center, Genève, Switzerland; Institute of Hematology, University of Foggia, Foggia, Italy; Institute of Pathology, Policlinico S. Orsola, Bologna, Italy; Leukemia Research Fund (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; and Oncology Research Unit and the University of Sydney Department of Pediatrics and Child's Health, The Children's Hospital at Westmead, NSW, Australia.

We generated a murine monoclonal antibody (B28p) detecting an antigenic determinant shared by the immunoglobulin superfamily receptor translocation-associated 1 (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 lymphohematopoietic tissues was restricted to B cells and plasma cells and clearly differed from that expected for IRTA1 (selectively expressed by mucosa-associated lymphoid tissue [MALT] marginal zone B cells). Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE)/mass-spectrometry analysis identified the 28-kDa protein as human tumor protein D52 (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 (paired box 5 [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 Ca2+-dependent manner, suggesting that these molecules may act in concert to regulate secretory processes in plasma cells, similarly to what was observed in pancreatic acinar cells. Finally, the anti-TPD52 monoclonal antibody served as a valuable tool for the diagnosis of B-cell malignancies.


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