Biased Use of the IGHV4 Family and Evidence for Antigen Selection in Chlamydophila Psittaci-negative Ocular Adnexal Extranodal Marginal Zone Lymphomas

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Jan 5

PMID 22216179

Citations 14

Authors

Daxing Zhu

Chen Lossos

Jennifer R Chapman-Fredricks

Julie M Matthews

Offiong F Ikpatt

Phillip Ruiz

Izidore S Lossos

Affiliations

Soon will be listed here.

Abstract

Extranodal marginal zone lymphomas (EMZL) are the most common lymphomas in the ocular adnexa. The etiology and potential role for antigenic stimulation in these lymphomas are still controversial. We have examined IGHV gene usage and mutations in 67 Chlamydophila psittaci-negative ocular adnexal EMZL. Clonal IGHV gene sequences were identified in 43 tumors originating from the orbit (19), conjunctivae (18) and lacrimal gland (6). Forty four potentially functional clonal IGHV gene sequences were detected with overrepresentation of the IGHV4 family and IGHV4-34 gene. All but 3 sequences were mutated with the average percent homology to the germ line of 93.5±6.1. Multinomial model and Focused binomial test demonstrated evidence for positive and/or negative antigen selection in 59% of the potentially functional IGHV genes. Intraclonal variation was detected in 8 of 11 tumor specimens. Overall our findings demonstrate that C. psittaci-negative ocular adnexal EMZL exhibit biased usage of IGHV families and genes with evidence for intraclonal heterogeneity and antigen selection in multiple tumors, implicating B-cell receptor-mediated antigen stimulation in the pathogenesis of these lymphomas.

Citing Articles

Distinct groups of autoantigens as drivers of ocular adnexal MALT lymphoma pathogenesis.

Bende R, Donner N, Wormhoudt T, Beentjes A, Scantlebery A, Grobben M Life Sci Alliance. 2024; 7(9).

PMID: 38977312 PMC: 11231493. DOI: 10.26508/lsa.202402841.

Clinical relevance of molecular aspects in extranodal marginal zone lymphoma: a critical appraisal.

Raderer M, Kiesewetter B, Du M Ther Adv Med Oncol. 2023; 15:17588359231183565.

PMID: 37389189 PMC: 10302523. DOI: 10.1177/17588359231183565.

Sequencing the B Cell Receptor Repertoires of Antibody-Deficient Individuals With and Without Infection Susceptibility.

Lim Y, Ramirez N, Asensio M, Chiang Y, Muller G, Mrovecova P J Clin Immunol. 2023; 43(5):940-950.

PMID: 36826743 PMC: 10276080. DOI: 10.1007/s10875-023-01448-0.

Gastric Cancer Pre-Stage Detection and Early Diagnosis of Gastritis Using Serum Protein Signatures.

Aziz S, Rasheed F, Zahra R, Konig S Molecules. 2022; 27(9).

PMID: 35566209 PMC: 9099457. DOI: 10.3390/molecules27092857.

The Biology of Ocular Adnexal Marginal Zone Lymphomas.

Johansson P, Eckstein A, Kuppers R Cancers (Basel). 2022; 14(5).

PMID: 35267569 PMC: 8908984. DOI: 10.3390/cancers14051264.

References

Tierens A, Delabie J, Michiels L, Vandenberghe P, De Wolf-Peeters C . Marginal-zone B cells in the human lymph node and spleen show somatic hypermutations and display clonal expansion. Blood. 1998; 93(1):226-34. View

Bhat N, Bieber M, Hsu F, Chapman C, Spellerberg M, Stevenson F . Rapid cytotoxicity of human B lymphocytes induced by VH4-34 (VH4.21) gene-encoded monoclonal antibodies, II. Clin Exp Immunol. 1997; 108(1):151-9. PMC: 1904638. DOI: 10.1046/j.1365-2249.1997.d01-976.x. View

Chanudet E, Zhou Y, Bacon C, Wotherspoon A, Muller-Hermelink H, Adam P . Chlamydia psittaci is variably associated with ocular adnexal MALT lymphoma in different geographical regions. J Pathol. 2006; 209(3):344-51. DOI: 10.1002/path.1984. View

Mulder M, Heddema E, Pannekoek Y, Faridpooya K, Oud M, Schilder-Tol E . No evidence for an association of ocular adnexal lymphoma with Chlamydia psittaci in a cohort of patients from the Netherlands. Leuk Res. 2006; 30(10):1305-7. DOI: 10.1016/j.leukres.2005.12.003. View

Bahler D, Szankasi P, Kulkarni S, Tubbs R, Cook J, Swerdlow S . Use of similar immunoglobulin VH gene segments by MALT lymphomas of the ocular adnexa. Mod Pathol. 2009; 22(6):833-8. PMC: 2723997. DOI: 10.1038/modpathol.2009.42. View

Martin A, Bardwell P, Woo C, Fan M, Shulman M, Scharff M . Activation-induced cytidine deaminase turns on somatic hypermutation in hybridomas. Nature. 2002; 415(6873):802-6. DOI: 10.1038/nature714. View

Lossos I, Alizadeh A, Eisen M, Chan W, Brown P, Botstein D . Ongoing immunoglobulin somatic mutation in germinal center B cell-like but not in activated B cell-like diffuse large cell lymphomas. Proc Natl Acad Sci U S A. 2000; 97(18):10209-13. PMC: 27813. DOI: 10.1073/pnas.180316097. View

Bessudo A, Rassenti L, Havlir D, Richman D, Feigal E, Kipps T . Aberrant and unstable expression of immunoglobulin genes in persons infected with human immunodeficiency virus. Blood. 1998; 92(4):1317-23. View

Hyjek E, Isaacson P . Primary B cell lymphoma of the thyroid and its relationship to Hashimoto's thyroiditis. Hum Pathol. 1988; 19(11):1315-26. DOI: 10.1016/s0046-8177(88)80287-9. View

10.

Mannami T, Yoshino T, Oshima K, Takase S, Kondo E, Ohara N . Clinical, histopathological, and immunogenetic analysis of ocular adnexal lymphoproliferative disorders: characterization of malt lymphoma and reactive lymphoid hyperplasia. Mod Pathol. 2001; 14(7):641-9. DOI: 10.1038/modpathol.3880366. View

11.

Lossos I, Okada C, Tibshirani R, Warnke R, Vose J, Greiner T . Molecular analysis of immunoglobulin genes in diffuse large B-cell lymphomas. Blood. 2000; 95(5):1797-803. View

12.

Brezinschek H, Brezinschek R, Lipsky P . Analysis of the heavy chain repertoire of human peripheral B cells using single-cell polymerase chain reaction. J Immunol. 1995; 155(1):190-202. View

13.

Thiede C, Alpen B, Morgner A, Schmidt M, Ritter M, Ehninger G . Ongoing somatic mutations and clonal expansions after cure of Helicobacter pylori infection in gastric mucosa-associated lymphoid tissue B-cell lymphoma. J Clin Oncol. 1998; 16(12):3822-31. DOI: 10.1200/JCO.1998.16.12.3822. View

14.

Thompsett A, Ellison D, Stevenson F, Zhu D . V(H) gene sequences from primary central nervous system lymphomas indicate derivation from highly mutated germinal center B cells with ongoing mutational activity. Blood. 1999; 94(5):1738-46. View

15.

Cook G, Tomlinson I . The human immunoglobulin VH repertoire. Immunol Today. 1995; 16(5):237-42. DOI: 10.1016/0167-5699(95)80166-9. View

16.

Coupland S, Foss H, Anagnostopoulos I, Hummel M, STEIN H . Immunoglobulin VH gene expression among extranodal marginal zone B-cell lymphomas of the ocular adnexa. Invest Ophthalmol Vis Sci. 1999; 40(3):555-62. View

17.

Hara Y, Nakamura N, KUZE T, Hashimoto Y, Sasaki Y, Shirakawa A . Immunoglobulin heavy chain gene analysis of ocular adnexal extranodal marginal zone B-cell lymphoma. Invest Ophthalmol Vis Sci. 2001; 42(11):2450-7. View

18.

Daibata M, Nemoto Y, Togitani K, Fukushima A, Ueno H, Ouchi K . Absence of Chlamydia psittaci in ocular adnexal lymphoma from Japanese patients. Br J Haematol. 2006; 132(5):651-2. DOI: 10.1111/j.1365-2141.2005.05943.x. View

19.

Ruiz A, Reischl U, Swerdlow S, Hartke M, Streubel B, Procop G . Extranodal marginal zone B-cell lymphomas of the ocular adnexa: multiparameter analysis of 34 cases including interphase molecular cytogenetics and PCR for Chlamydia psittaci. Am J Surg Pathol. 2007; 31(5):792-802. DOI: 10.1097/01.pas.0000249445.28713.88. View

20.

Wotherspoon A, Ortiz-Hidalgo C, Falzon M, Isaacson P . Helicobacter pylori-associated gastritis and primary B-cell gastric lymphoma. Lancet. 1991; 338(8776):1175-6. DOI: 10.1016/0140-6736(91)92035-z. View