High expression of the inhibitory receptor BTLA in T-follicular helper cells and in B-cell small lymphocytic lymphoma/chronic lymphocytic leukemia.
B- and T-lymphocyte attenuator (BTLA) is a lymphoid receptor that inhibits lymphocyte activation on interaction with its ligand, herpesvirus entry mediator (HVEM). We developed monoclonal antibodies against BTLA and HVEM to study their expression using immunohistochemical and flow cytometric analyses in human tissues. In reactive lymph nodes, they were both expressed in interfollicular T cells and in B cells from mantle and marginal zones. Within germinal centers, B cells were negative, whereas T follicular helper (TFH) cells were BTLA+ and follicular dendritic cells were HVEM+. BTLA was strongly expressed in chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL, 19 of 19 positive) when compared with other small B-cell lymphomas, including follicular lymphoma (0 of 24 positive), mantle cell lymphoma (0 of 10 positive), and marginal zone lymphoma (0 of 5 positive). Our results suggest that down-regulation of the BTLA-HVEM pathway may be involved in germinal center B-cell activation. The specific high expression of BTLA in B-CLL/SLL represents a new potential diagnostic tool. The BTLA positivity of TFH cells may be a basis for designing future immunotherapies.
M'Hidi
Hasni
H
Departments of Bio-pathology, Paoli-Calmettes Institute, Marseille, France.
Thibult
Marie-Laure
ML
Chetaille
Bruno
B
Rey
Françoise
F
Bouadallah
Reda
R
Nicollas
Richard
R
Olive
Daniel
D
Xerri
Luc
L
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015536:Down-Regulation; D006801:Humans; D007150:Immunohistochemistry; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D051379:Mice; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
C482586:BTLA protein, human; D011971:Receptors, Immunologic; D053240:Receptors, Tumor Necrosis Factor, Member 14; C506028:TNFRSF14 protein, human