TY - JOUR
T1 - Immunoglobulin gene repertoire diversification and selection in the stomach - from gastritis to gastric lymphomas
AU - Michaeli, Miri
AU - Tabibian-Keissar, Hilla
AU - Schiby, Ginette
AU - Shahaf, Gitit
AU - Pickman, Yishai
AU - Hazanov, Lena
AU - Rosenblatt, Kinneret
AU - Dunn-Walters, Deborah K.
AU - Barshack, Iris
AU - Mehr, Ramit
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - B-cells
KW - DLBCL
KW - Gastritis
KW - H. pylori
KW - Ig gene
KW - MALT lymphoma
KW - Repertoire
KW - Somatic hypermutation
UR - http://www.scopus.com/inward/record.url?scp=84905649836&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2014.00264
DO - 10.3389/fimmu.2014.00264
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C2 - 24917868
SN - 1664-3224
VL - 5
JO - Frontiers in Immunology
JF - Frontiers in Immunology
IS - JUN
M1 - 264
ER -