Immunoglobulin gene repertoire diversification and selection in the stomach – from gastritis to gastric lymphomas

• Main Authors: Miri eMichaeli, Hilla eTabibian-Keissar, Ginette eSchiby, Gitit eShahaf, Yishai ePickman, Lena eHazanov, Kinneret eRosenblatt, Deborah K Dunn-Walters, Iris eBarshack, Ramit eMehr
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2014-06-01
• Series: Frontiers in Immunology
• Subjects: Gastritis; DLBCL; H. pylori; somatic hypermutation; B-cells; repertoire
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00264/full

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. <br/>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 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.