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Analysis of Somatic Hypermutation in the JH4 intron of Germinal Center B cells from Mouse Peyer's Patches
Published on: April 20, 2021
Gastric MALT lymphoma B cells express polyreactive, somatically mutated immunoglobulins
Vanessa J Craig1, Isabelle Arnold, Christiane Gerke
1Institute of Molecular Cancer Research, University of Zürich, Zürich, Switzerland.
Blood
|December 8, 2009
Summary
Gastric MALT lymphoma, often caused by Helicobacter pylori, involves B-cell receptor stimulation by various antigens. This study reveals polyreactive antibodies in both human and mouse models, suggesting a role for self- and foreign antigens in MALT lymphoma development.
Area of Science:
- Immunology
- Oncology
- Microbiology
Background:
- Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is linked to chronic Helicobacter pylori infection and inflammation.
- The human MALT lymphoma can be modeled in BALB/c mice infected with Helicobacter.
- Understanding the antibody characteristics and antigen specificity is crucial for MALT lymphoma research.
Purpose of the Study:
- To analyze antibody sequences and antigen specificity in murine and human MALT lymphoma.
- To investigate the role of somatic hypermutation and selection pressures in MALT lymphoma development.
- To explore the potential involvement of self- and foreign antigens in MALT lymphoma pathogenesis.
Main Methods:
- Analysis of antibody sequences from MALT lymphoma-derived antibodies in humans and mice.
- Recombinant expression of MALT lymphoma antibodies.
- Assessment of antigen binding specificity using enzyme-linked immunosorbent assays (ELISAs).
- Competitive binding assays to determine antigen blockade.
Main Results:
- Most human and murine MALT lymphomas were monoclonal.
- Immunoglobulin heavy chain genes showed somatic hypermutation, with evidence of intraclonal variation and selection.
- MALT lymphoma antibodies exhibited intermediate affinity binding to diverse self- and foreign antigens, including Helicobacter, IgG, DNA, and stomach extract.
- A bias towards V(H) gene segments associated with autoantibodies and polyreactivity was observed.
Conclusions:
- MALT lymphoma development may be driven by stimulation from various local self- and foreign antigens via the B-cell receptor.
- Polyreactive antibodies play a significant role in MALT lymphoma pathogenesis.
- The findings provide insights into the antigenic stimulation mechanisms underlying MALT lymphoma.
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