AUTHOR=Michaeli Miri , Tabibian-Keissar Hilla , Schiby Ginette , Shahaf Gitit , Pickman Yishai , Hazanov Lena , Rosenblatt Kinneret , Dunn-Walters Deborah K. , Barshack Iris , Mehr Ramit 

TITLE=Immunoglobulin Gene Repertoire Diversification and Selection in the Stomach – From Gastritis to Gastric Lymphomas

JOURNAL=Frontiers in Immunology

VOLUME=5

YEAR=2014

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2014.00264

DOI=10.3389/fimmu.2014.00264

ISSN=1664-3224

ABSTRACT=<p>Chronic gastritis is characterized by gastric mucosal inflammation due to autoimmune responses or infection, frequently with <italic>Helicobacter pylori</italic>. Gastritis with <italic>H. pylori</italic> 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 <italic>de novo</italic>. 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 <italic>H. pylori</italic>) 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.</p>