Role of non- Helicobacter pylori gastric Helicobacters in helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma

Abstract

Marginal zone lymphomas rank as the third most prevalent form of non-Hodgkin B-cell lymphoma, trailing behind diffuse large B-cell lymphoma and follicular lymphoma. Gastric mucosa-associated lymphoid tissue lymphoma (GML) is a low-grade B-cell neoplasia frequently correlated with Helicobacter pylori (H. pylori)-induced chronic gastritis. On the other hand, a specific subset of individuals diagnosed with GML does not exhibit H. pylori infection. In contrast to its H. pylori-positive counterpart, it was previously believed that H. pylori-negative GML was less likely to respond to antimicrobial therapy. Despite this, surprisingly, in-creasing evidence supports that a considerable proportion of patients with H. pylori-negative GML show complete histopathological remission after bacterial eradication therapy. Nonetheless, the precise mechanisms underlying this treatment responsiveness are not yet fully comprehended. In recent years, there has been growing interest in investigating the role of non-H. pylori gastric helicobacters (NHPHs) in the pathogenesis of H. pylori-negative GML. However, additional research is required to establish the causal relationship between NHPHs and GML. In this minireview, we examined the current understanding and proposed prospects on the involvement of NHPHs in H. pylori-negative GML, as well as their potential response to bacterial eradication therapy.

Keywords: B cell; Gastric mucosa-associated lymphoid tissue lymphoma; Heli-cobacter heilmannii; Helicobacter pylori; Helicobacter suis; Lymphoma; Marginal zone; Non-Helicobacter pylori gastric helicobacters.

Figure 1

Antigen-induced acquisition of gastric mucosa-associated lymphoid tissue. A: Antigen-induced inflammation; B: Clonal expansion of B cells supported by specific T helper cells; C: Acquisition of mucosa-associated lymphoid tissue (MALT). In the presence of chronic antigenic stimulation, gastric mucosal cells undergo activation and produce proinflammatory cytokines. These molecular mediators play a crucial role in initiating and perpetuating an immune response within the gastric tissue. As a consequence, lymphoid cells are recruited and infiltrate the gastric tissue. This cascade of events ultimately culminates in the development of MALT. H. pylori: Helicobacter pylori; NHPHs: Non-Helicobacter pylori gastric helicobacters; DC: Dendritic cell; MΦ: Macrophage; TCR: T cell receptor; CD40: Cluster of differentiation 40; CD40L: Cluster of differentiation 40 Ligand; BCR: B cell receptor.

Figure 2

Simplified scheme of antigen-induced transformation of normal marginal-zone B-cells into malignant cells. A: Polyclonal B cell expansion and a selection process; B: Antigen-dependent monoclonal expansion; C: Acquisition of genetic abnormalities and antigen-independent lymphomagenesis. The proliferation of B cells is primarily induced by the interaction between CD40 and CD40 Ligand, facilitated by antigen-activated reactive T cells. Additionally, cytokines play a role in driving this B-cell proliferation. The persistent proliferative state of these B cells, along with chronic inflammation, triggers additional oncogenic events. Ultimately, these events lead to the development of antigen-independent lymphoproliferation. NHPHs: Non-Helicobacter pylori gastric helicobacters; ROS: Reactive oxygen species; MZL: Marginal zone lymphoma; MALT: Mucosa-associated lymphoid tissue; H. pylori: Helicobacter pylori.