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Blood, 15 November 2003, Vol. 102, No. 10, pp. 3684-3692.
Prepublished online as a Blood First Edition Paper on July 24, 2003; DOI 10.1182/blood-2003-03-0750.


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IMMUNOBIOLOGY

Expression of the IRTA1 receptor identifies intraepithelial and subepithelial marginal zone B cells of the mucosa-associated lymphoid tissue (MALT)

Brunangelo Falini, Enrico Tiacci, Alessandra Pucciarini, Barbara Bigerna, Julia Kurth, Georgia Hatzivassiliou, Sara Droetto, Barbara Verducci Galletti, Marcello Gambacorta, Attilio Orazi, Laura Pasqualucci, Ira Miller, Ralf Küppers, Riccardo Dalla-Favera, and Giorgio Cattoretti

From the Institutes of Hematology and Internal Medicine, University of Perugia, Perugia, Italy; Department of Internal Medicine I, University of Cologne, Cologne, Germany; Institute for Cancer Genetics and the Department of Pathology, Columbia University, New York, NY; Institute of Pathology, Niguarda Hospital, Milan, Italy; and Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN.

IRTA1 (immunoglobulin superfamily receptor translocation-associated 1) is a novel surface B-cell receptor related to Fc receptors, inhibitory receptor superfamily (IRS), and cell adhesion molecule (CAM) family members and we mapped for the first time its distribution in human lymphoid tissues, using newly generated specific antibodies. IRTA1 was selectively and consistently expressed by a B-cell population located underneath and within the tonsil epithelium and dome epithelium of Peyer patches (regarded as the anatomic equivalents of marginal zone). Similarly, in mucosa-associated lymphoid tissue (MALT) lymphomas IRTA1 was mainly expressed by tumor cells involved in lympho-epithelial lesions. In contrast, no or a low number of IRTA1+ cells was usually observed in the marginal zone of mesenteric lymph nodes and spleen. Interestingly, monocytoid B cells in reactive lymph nodes were strongly IRTA1+. Tonsil IRTA1+ cells expressed the memory B-cell marker CD27 but not mantle cell-, germinal center-, and plasma cell-associated molecules. Polymerase chain reaction (PCR) analysis of single tonsil IRTA1+ cells showed they represent a mixed B-cell population carrying mostly mutated, but also unmutated, IgV genes. The immunohistochemical finding in the tonsil epithelial areas of aggregates of IRTA1+ B cells closely adjacent to plasma cells surrounding small vessels suggests antigen-triggered in situ proliferation/differentiation of memory IRTA1+ cells into plasma cells. Collectively, these results suggest a role of IRTA1 in the immune function of B cells within epithelia. (Blood. 2003;102: 3684-3692)


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