Oligoclonal Expansions of T-Cell Repertoire in Gastric Mucosa Associated Lymphoid Tissue Type B-Cell Lymphoma and Adjacent Gastritis

Abstract

Local stimulation by Helicobacter pylori (HP), autoantigen, and a concurrent T-cell-mediated stimulation of B cells are believed to play an important role in gastric mucosa-associated lymphoid tissue (MALT) type B cell lymphomagenesis. Many autoimmune diseases have shown to lead to a skewed T-cell repertoire with autoantigen specific expansions and deletions. Characterization of lymphoma and gastritis areas of seven gastrectomy specimens using a T-cell receptor beta variable chain (TCR betaV) family-specific reverse transcriptase (RT)-polymerase chain reaction (PCR) assay and fluorescence-activated cell sorter (FACS) analysis revealed a local chronic and acute activation of T cells in lymphoma and an oligoclonal T-cell repertoire in gastritis and in lymphoma, partially sharing the same clones. Local activation and a partial identity suggest that an antigenic challenge caused by a common local pathogen may still continue to take place in MALT type lymphoma as in gastritis, consistent with the view that gastritis may be a precursor lesion of MALT type lymphoma. Expansions that were found only in one of the compartments suggest that also an immune hyperstimulation may contribute to the T-cell repertoire, possibly because of certain tissue antigens. Deletions of TCR betaV families found only in gastritis underline the view that autoantigen may play an important role in its pathogenesis.

Definition and characterization of the systemic T-cell dysregulation in untreated indolent B-cell lymphoma and very early CLL

“…28 Recently activated, CD69 ϩ or OX40 ϩ T helper cells were absent from the blood of our patients, whereas they abound at indolent lymphoma sites. [29][30][31] Some of these aberrantly activated T cells reenter the circulation, where they respond faster to immune receptor stimulation. On the other hand, these cells are already presenescent and prone to undergo apoptosis, facilitated by transcriptional upregulation of the apoptosis cascade.…”

The peripheral helper T-cell repertoire in untreated indolent B-cell lymphomas: evidence for antigen-driven lymphomagenesis

“…1 Consistent with this model, oligoclonal T-cell expansions occur in H. pylori-associated gastritis and consecutive MALT lymphoma. 2 Other MZL-associated organisms that presumably initiate an analogous lymphomagenesis are Chlamydia psittaci, Hepatitis C virus, Borrelia burgdorferi, and C. jejuni. 1 T-cellmediated development of B-cell lymphomas with similarity to MZL also occurs regularly in a transgenic mouse model when B-cell-specific, T H 2-biased T cells provide continuous growth signals.…”

“…1 Accordingly, experimentally induced reduction of global methylation levels increases tumour formation in mice under certain circumstances. 2 Somewhat contradictory, in patients with myelodysplastic syndrome (MDS), the induction of hypomethylation using DNA methyltransferase inhibitors leads to very promising clinical response rates and haematological improvement. 3 Therefore, we analysed the global methylation level in a large cohort of MDS patients comprising all subgroups (n ¼ 127), to figure out the molecular mechanisms underlying this unexpected finding.…”

An Immunohistochemical Analysis of Gastric B-cell Lymphomas: Stromal Cells Exhibit Peculiar Histogenesis in Gastric B-cell Lymphomas

“…On-going somatic hypermutation of the IgH gene variable region in MALT type lymphoma might be explained by the disordered antigen recognition in the NOrich microenvironment [19]. As for T-cells in HP infection, dominant th1 T-cells [4], loss of TCRBV6S1B function [32], oligoclonal expansions of T-cell repertoire [12], and highly variable T-cell responses to 60-kilodalton heat shock protein (HSP60) [50] were reported in HP infection. Expression of iNOS was also found in stromal cells in the paracortex of the regional lymph nodes in the stomach with HP infection [20].…”

“…This study analyzed immunological phenotypes of stromal cells in gBL and found an increase of dendritic cells (DC) that were positive for CD68 and expressed thymidine phosphorylase (TP) [16] in many cases. Because synovial cells can express TP under Tcell stimulation [42,57], anti-HP T-cell immunity [4,12,32,45,50,56] may induce many T-cell-associated DC expressing TP in the background of gBL. On the other hand, we speculated that lipopolysaccharides (LPS) of HP bodies, Lewis X and Y, indirectly induced a nitric oxide (NO)-rich microenvironment in germinal centers (GC) in the regional lymph nodes [17] of the stomach with HP-related peptic ulcers [20].…”