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Leukemia (2012) 26, 1647 -- 1653& 2012 Macmillan Publishers Limited All rights reserved 0887-6924/12
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ORIGINAL ARTICLE
Chlamydia psittaci-negative ocular adnexal marginal zone B-cell lymphomas have biased VH4-34 immunoglobulin gene expression and proliferate in a distinct inammatory environment
F van Maldegem1, TAM Wormhoudt1, MMS Mulder1, MECM Oud1, E Schilder-Tol1, AR Musler1, J Aten1, P Saeed2, MJ Kersten3, ST Pals1, CJM van Noesel1 and RJ Bende1
Ocular adnexal marginal zone B-cell lymphomas (OAMZLs) arise in the connective tissues of the orbit or in the mucosa-associated lymphoid tissue of the conjunctiva. Here, we present the immunological and genetic analyses of 20 primary Chlamydia psittaci (Cp)-negative OAMZLs. Analysis of the immunoglobulin variable heavy chain (IgVH) gene usage demonstrated a signicant preference for VH4-34. A combined analysis across all previously published OAMZLs conrmed that this is a general feature of OAMZL, in particular of the Cp-negative group. Our series of OAMZLs did not express the characteristic rheumatoid factor VHDJH rearrangements that were previously found in salivary gland- and gastric-marginal zone B-cell lymphomas (MZBCLs). We did not detect the MZBCL-specic chromosomal translocations, t(11;18) API2-MALT1 (mucosa-associated lymphoid tissue1) and t(14;18) IgH/MALT1. Two cases contained a premature stop codon in the A20 gene (TNFAIP3) and one case harbored the activating MYD88 hotspot mutation L265P. Variable nuclear expression of BCL10, NFkB1 (p50) and NFkB2 (p52)
suggests that other additional genetic abnormalities affecting the NFkB pathway exist within this group of lymphomas. OAMZL showed variable expression of the chemokine receptor CXCR3 and integrin a4b7 by the tumor B cells, and low interferon-g and interlukin-4 mRNA levels in the tissue, indicative of an inammatory environment with features in between those previously found in cutaneous and other extranodal MZBCL. The strongly biased usage of VH4-34 in Cp-negative OAMZLs suggests involvement of a particular stimulatory (auto-) antigen in their development.
Leukemia (2012) 26, 1647--1653; doi:http://dx.doi.org/10.1038/leu.2012.28
Web End =10.1038/leu.2012.28
Keywords: B-cell lymphoma; B cells; immunoglobulin; translocations; inammation
INTRODUCTIONExtranodal marginal zone B-cell lymphomas (MZBCLs) generally arise at sites of acquired mucosa-associated lymphoid tissue (MALT) and are associated with persistent infections such as Helicobacter pylori gastritis, or with organ-specic autoimmune diseases like Sjgrens syndrome.1 In general, MZBCLs express somatically mutated immunoglobulin variable region (IgV) genes, mostly of the IgM isotype. Selection against replacement mutations in the framework...