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A Colorimetric Assay that Specifically Measures Granzyme B Proteolytic Activity: Hydrolysis of Boc-Ala-Ala-Asp-S-Bzl
Published on: November 28, 2014
Activated mouse B cells lack expression of granzyme B
Magdalena Hagn1, Gabrielle T Belz, Axel Kallies
1Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria 3002, Australia.
Journal of Immunology (Baltimore, Md. : 1950)
|March 20, 2012
Summary
Human B cells express granzyme B (GrB), but mice do not. Studies in mice failed to detect GrB in B cells, indicating mouse models are unsuitable for studying human B cell GrB functions.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Human B cells have been reported to express and secrete granzyme B (GrB) upon stimulation.
- The precise function of GrB in B cell biology remains largely unknown.
- Investigating GrB in B cells could offer insights into immune responses.
Purpose of the Study:
- To investigate the expression and activity of granzyme B (GrB) in mouse B cells.
- To determine if mouse models can be used to study the role of GrB in human B cell biology.
- To assess the necessity of GrB for humoral immune responses.
Main Methods:
- Assaying for granzyme B (GrB) expression and proteolytic activity in various mouse strains (C57BL/6, DBA/2, CBA, BALB/c) under different stimulation conditions.
- In vivo studies involving influenza virus and murine gamma-herpesvirus infections to assess GrB expression in B cells and CTLs.
- Evaluating antibody production, affinity maturation, and secondary responses in GrB-deficient mice using a model antigen.
Main Results:
- Granzyme B (GrB) expression or proteolytic activity was not detected in mouse B cells, even with specific stimuli or during viral infections.
- GrB-deficient mice exhibited normal antibody production, affinity maturation, and secondary responses, indicating GrB redundancy in humoral immunity.
- Viral infections induced GrB in cytotoxic T lymphocytes (CTLs) but not in B cells in mice.
Conclusions:
- Mouse models are not suitable for studying the physiological consequences of granzyme B (GrB) expression in human B cells due to significant evolutionary differences in immune systems.
- Granzyme B (GrB) is redundant for antibody responses in mice.
- The role and physiological consequences of GrB in human B cells require further investigation using human-specific models.
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