title: Immunoglobulin gene repertoire diversification and selection in the stomach - from gastritis to gastric lymphomas.
abstract: Chronic gastritis is characterized by gastric mucosal inflammation due to autoimmune responses or infection, frequently with Helicobacter pylori. Gastritis with H. pylori background can cause gastric mucosa-associated lymphoid tissue lymphoma (MALT-L), which sometimes further transforms into diffuse large B-cell lymphoma (DLBCL). However, gastric DLBCL can also be initiated de novo. The mechanisms underlying transformation into DLBCL are not completely understood. We analyzed immunoglobulin repertoires and clonal trees to investigate whether and how immunoglobulin gene repertoires, clonal diversification, and selection in gastritis, gastric MALT-L, and DLBCL differ from each other and from normal responses. The two gastritis types (positive or negative for H. pylori) had similarly diverse repertoires. MALT-L dominant clones (defined as the largest clones in each sample) presented higher diversification and longer mutational histories compared with all other conditions. DLBCL dominant clones displayed lower clonal diversification, suggesting the transforming events are triggered by similar responses in different patients. These results are surprising, as we expected to find similarities between the dominant clones of gastritis and MALT-L and between those of MALT-L and DLBCL.
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University , Ramat Gan , Israel.
authors.forename: Miri
authors.initials: M
authors.lastname: Michaeli
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University , Ramat Gan , Israel ; Department of Pathology, Sheba Medical Center , Ramat Gan , Israel.
authors.forename: Hilla
authors.initials: H
authors.lastname: Tabibian-Keissar
authors.affiliation: Department of Pathology, Sheba Medical Center , Ramat Gan , Israel.
authors.forename: Ginette
authors.initials: G
authors.lastname: Schiby
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University , Ramat Gan , Israel.
authors.forename: Gitit
authors.initials: G
authors.lastname: Shahaf
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University , Ramat Gan , Israel.
authors.forename: Yishai
authors.initials: Y
authors.lastname: Pickman
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University , Ramat Gan , Israel.
authors.forename: Lena
authors.initials: L
authors.lastname: Hazanov
authors.affiliation: Department of Pathology, Sheba Medical Center , Ramat Gan , Israel.
authors.forename: Kinneret
authors.initials: K
authors.lastname: Rosenblatt
authors.affiliation: Division of Immunology, Infection, and Inflammatory Diseases, King's College London School of Medicine , London , UK.
authors.forename: Deborah K
authors.initials: DK
authors.lastname: Dunn-Walters
authors.affiliation: Department of Pathology, Sheba Medical Center , Ramat Gan , Israel ; Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv , Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Barshack
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University , Ramat Gan , Israel.
authors.forename: Ramit
authors.initials: R
authors.lastname: Mehr
keywords: B-cells; DLBCL; H. pylori; Ig gene; MALT lymphoma; gastritis; repertoire; somatic hypermutation