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Enteroantigen (eAg)-binding B lymphocytes in the mouse - phenotype, distribution, function and eAg-specific antibody
Freja Albjerg Venning1, Mette Louise Trempenau, Esben Schmidt
1Laboratory of Experimental Immunology, Department of International Health, Immunology and Microbiology, The Panum Institute, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Summary
Regulatory B cells (B cells) that bind enteroantigen (eAg) play a key role in controlling colitis. These eAg+ B cells are potent antigen-presenting cells and secrete anti-inflammatory IL-10, suggesting therapeutic potential.
Area of Science:
- Immunology
- Autoimmune Diseases
- Gastroenterology
Background:
- Accumulating evidence suggests beneficial roles for B lymphocytes in autoimmune diseases.
- Specific B cell subsets are increasingly recognized for their regulatory functions.
- Previous studies indicated a regulatory effect of B cells in a T cell transfer model of colitis.
Purpose of the Study:
- To investigate the role of enteroantigen-binding B cells (eAg+ B cells) in the immunopathology of colitis.
- To characterize the properties and functions of eAg+ B cells.
- To explore the involvement of the B cell receptor (BCR) in eAg binding and T cell stimulation.
Main Methods:
- Detection and characterization of eAg+ B cells in mouse peripheral lymphoid organs.
- Assessment of eAg+ B cell antigen-presenting capacity for T cell proliferation.
- Measurement of IL-10 secretion by eAg+ B cells in vitro.
- Comparison of eAg binding and T cell stimulatory activity between wild-type and BCR transgenic B cells.
- Generation of hybridoma cells secreting eAg-specific antibodies.
Main Results:
- eAg+ B cells, including B2 and B1 lineages, were identified in all peripheral lymphoid organs.
- eAg+ B cells demonstrated superior efficiency in presenting eAg and inducing T cell proliferation compared to unfractionated splenocytes or eAg- B cells.
- eAg+ B cells secreted significantly more IL-10 in vitro than eAg- B cells, indicating anti-inflammatory potential.
- BCR transgenic B cells exhibited reduced eAg binding and T cell stimulatory activity.
- Approximately 10% of hybridoma cells generated from eAg-activated B cells secreted eAg-specific antibodies.
Conclusions:
- A distinct subset of eAg+ B cells exists and possesses potent antigen-presenting and regulatory functions.
- These eAg+ B cells may play a crucial role in modulating immune responses in colitis.
- The B cell receptor is implicated in the binding and processing of eAg.
- eAg+ B cells represent a potential target for therapeutic interventions in autoimmune diseases like colitis.
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