Expression of the IRTA1 receptor identifies intraepithelial and subepithelial marginal zone B cells of the mucosa-associated lymphoid tissue (MALT).
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.
Falini
Brunangelo
B
Institute of Hematology, University of Perugia, 06122 Perugia, Italy. faliniem@unipg.it
Tiacci
Enrico
E
Pucciarini
Alessandra
A
Bigerna
Barbara
B
Kurth
Julia
J
Hatzivassiliou
Georgia
G
Droetto
Sara
S
Galletti
Barbara Verducci
BV
Gambacorta
Marcello
M
Orazi
Attilio
A
Pasqualucci
Laura
L
Miller
Ira
I
Kuppers
Ralf
R
Dalla-Favera
Riccardo
R
Cattoretti
Giorgio
G
D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000737:chemistry*; D004847:Epithelial Cells / Q000737:chemistry*; D005803:Genes, Immunoglobulin / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000166:cytology; D018442:Lymphoma, B-Cell, Marginal Zone / Q000473:pathology*; D014066:Palatine Tonsil / Q000166:cytology; D010581:Peyer's Patches / Q000166:cytology; D010950:Plasma Cells / Q000166:cytology; D011971:Receptors, Immunologic / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D013154:Spleen / Q000166:cytology; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; C480028:IRTA1 protein, mouse; D011971:Receptors, Immunologic