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T cells and natural killer cells regulate human IgG subclass concentrations in SCID mice
D M Ambrosino1, M Wang, A Ciamarra
1Laboratory of Infectious Diseases, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Cellular Immunology
|April 15, 1994
Summary
T cells and natural killer (NK) cells significantly influence human immunoglobulin G (IgG) subclass production. This study in severe combined immunodeficient (SCID) mice reveals their critical role in regulating IgG subclass concentrations.
Area of Science:
- Immunology
- Cell Biology
Background:
- Human immunoglobulin G (IgG) subclass regulation by cytokines is not fully understood.
- T cells and natural killer (NK) cells are known producers of key cytokines like IL-4 and IFN-gamma.
Purpose of the Study:
- To investigate the impact of T cells and NK cells on human IgG subclass production.
- To utilize a humanized severe combined immunodeficient (SCID) mouse model for studying IgG subclass regulation.
Main Methods:
- Severe combined immunodeficient (SCID) mice were reconstituted with human B-cell-enriched splenocytes, with or without T cells.
- The effect of CD16+ (NK) cells was assessed by depleting them from preparations.
- Human IgG subclass concentrations (IgG1, IgG2, IgG3, IgG4) were measured in mouse serum.
Main Results:
- Mice receiving B cells plus T cells showed significantly higher IgG concentrations and IgG1/IgG2 ratios compared to B cells alone.
- In the absence of T cells, IgG2 constituted a significantly higher percentage (58%) of total IgG compared to when T cells were present (19%).
- Depletion of NK cells led to a twofold increase in IgG2 concentrations, while other IgG subclasses remained unaffected.
Conclusions:
- T cells and NK cells play a significant role in the regulation of human IgG subclass production.
- The SCID mouse model is a valuable tool for further investigating the mechanisms of human IgG subclass regulation.