BAFF Blockade Attenuates B Cell MALT Formation in Conditional Nlrc5-Deficient Mice With Helicobacter felis Infection

Area of Science:

• Immunology
• Gastroenterology
• Oncology

Background:

• Helicobacter infection is a primary cause of gastric mucosa-associated lymphoid tissue (MALT) lymphoma.
• B cell-activating factor (BAFF) is crucial for B cell proliferation and implicated in various B cell disorders.

Purpose of the Study:

• To investigate the role of BAFF in Helicobacter-induced gastric MALT lymphoma using a mouse model with conditional knockout of NOD-like receptor family CARD domain-containing 5 (Nlrc5).

Main Methods:

• Utilized Helicobacter felis infection in Nlrc5 conditional knockout mice.
• Administered BAFF signaling blockade before and after gastritis onset.
• Analyzed gastric immune cell populations and BAFF transcript variants in macrophages.

Main Results:

• Helicobacter felis infection significantly increased gastric BAFF production in Nlrc5-deficient mice.
• BAFF blockade markedly reduced MALT development, gastric B cell follicles, and gland hyperplasia.
• BAFF inhibition altered the gastric immune cell landscape and identified TNFSF13B (BAFF)-206 as a key upregulated transcript.

Conclusions:

• The NLRC5-BAFF signaling axis is implicated in Helicobacter-induced gastric B cell MALT lymphoma.
• Targeting BAFF signaling presents a promising therapeutic strategy for this malignancy.