TY - JOUR
T1 - Immunoglobulin gene repertoire in ocular adnexal lymphomas
T2 - Hints on the nature of the antigenic stimulation
AU - Dagklis, A.
AU - Ponzoni, M.
AU - Govi, S.
AU - Cangi, M. G.
AU - Pasini, E.
AU - Charlotte, F.
AU - Vino, A.
AU - Doglioni, C.
AU - Davì, F.
AU - Lossos, I. S.
AU - Ntountas, I.
AU - Papadaki, T.
AU - Dolcetti, R.
AU - Ferreri, A. J.M.
AU - Stamatopoulos, K.
AU - Ghia, P.
N1 - Funding Information:
This work was in part supported by Associazione Italiana per la Ricerca sul Cancro (AIRC, Milan, to PG and RD), Progetti di Ricerca di Interesse Nazionale (PRIN), Progetto Integrato Onco-logia (PIO), Fondazione CARIPLO, Milan; and the ENosAI project (code 09SYN-13-880), co-funded by the EU and the Hellenic General Secretariat for Research and Technology (to KS). Elisa Pasini is a fellow of the Fondazione Italiana per la Ricerca sul Cancro (FIRC).
PY - 2012/4
Y1 - 2012/4
N2 - Evidence from certain geographical areas links lymphomas of the ocular adnexa marginal zone B-cell lymphomas (OAMZL) with Chlamydophila psittaci (Cp) infection, suggesting that lymphoma development is dependent upon chronic stimulation by persistent infections. Notwithstanding that, the actual immunopathogenetical mechanisms have not yet been elucidated. As in other B-cell lymphomas, insight into this issue, especially with regard to potential selecting ligands, could be provided by analysis of the immunoglobulin (IG) receptors of the malignant clones. To this end, we studied the molecular features of IGs in 44 patients with OAMZL (40% Cp-positive), identifying features suggestive of a pathogenic mechanism of autoreactivity. Herein, we show that lymphoma cells express a distinctive IG repertoire, with electropositive antigen (Ag)-binding sites, reminiscent of autoantibodies (auto-Abs) recognizing DNA. Additionally, five (11%) cases of OAMZL expressed IGs homologous with autoreactive Abs or IGs of patients with chronic lymphocytic leukemia, a disease known for the expression of autoreactive IGs by neoplastic cells. In contrast, no similarity with known anti-Chlamydophila Abs was found. Taken together, these results strongly indicate that OAMZL may originate from B cells selected for their capability to bind Ags and, in particular, auto-Ags. In OAMZL associated with Cp infection, the pathogen likely acts indirectly on the malignant B cells, promoting the development of an inflammatory milieu, where auto-Ags could be exposed and presented, driving proliferation and expansion of self-reactive B cells.
AB - Evidence from certain geographical areas links lymphomas of the ocular adnexa marginal zone B-cell lymphomas (OAMZL) with Chlamydophila psittaci (Cp) infection, suggesting that lymphoma development is dependent upon chronic stimulation by persistent infections. Notwithstanding that, the actual immunopathogenetical mechanisms have not yet been elucidated. As in other B-cell lymphomas, insight into this issue, especially with regard to potential selecting ligands, could be provided by analysis of the immunoglobulin (IG) receptors of the malignant clones. To this end, we studied the molecular features of IGs in 44 patients with OAMZL (40% Cp-positive), identifying features suggestive of a pathogenic mechanism of autoreactivity. Herein, we show that lymphoma cells express a distinctive IG repertoire, with electropositive antigen (Ag)-binding sites, reminiscent of autoantibodies (auto-Abs) recognizing DNA. Additionally, five (11%) cases of OAMZL expressed IGs homologous with autoreactive Abs or IGs of patients with chronic lymphocytic leukemia, a disease known for the expression of autoreactive IGs by neoplastic cells. In contrast, no similarity with known anti-Chlamydophila Abs was found. Taken together, these results strongly indicate that OAMZL may originate from B cells selected for their capability to bind Ags and, in particular, auto-Ags. In OAMZL associated with Cp infection, the pathogen likely acts indirectly on the malignant B cells, promoting the development of an inflammatory milieu, where auto-Ags could be exposed and presented, driving proliferation and expansion of self-reactive B cells.
KW - Chlamydia psittaci
KW - immunoglobulins
KW - ocular adnexa lymphoma
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U2 - 10.1038/leu.2011.276
DO - 10.1038/leu.2011.276
M3 - Article
C2 - 22024723
AN - SCOPUS:84859634374
VL - 26
SP - 814
EP - 821
JO - Leukemia
JF - Leukemia
SN - 0887-6924
IS - 4
ER -