A single autosomal gene defect severely limits IgG but not IgM responses in B lymphocyte-deficient A/WySnJ mice
✍ Scribed by David J. Miller; Keith D. Hanson; Julie A. Carman; Colleen E. Hayes
- Book ID
- 102828020
- Publisher
- John Wiley and Sons
- Year
- 1992
- Tongue
- English
- Weight
- 717 KB
- Volume
- 22
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Defective IgG memory in B cell-deficient AIWySnJ mice 373 A single autosomal gene defect severely limits IgG but not IgM responses in B lymphocyte-deficient ANVySnJ mice* Antigen-stimulated B lymphocytes either differentiate into IgM-secreting plasma cells or into memory B cells that secrete other immunoglobulin isotypes upon antigen restimulation. The mechanisms that generate and maintain memory B cells are poorly understood. Previously, we described a severe B lymphocyte deficiency in adult strain A/WySnJ mice compared to subline AIJ. Here we show that the single, autosomal co-dominant locus responsible for the deficiency also diminishes IgG-secreting B cell formation without interfering with IgM-secreting plasma cell differentiation. A/WySnJ secondary IgGl responses to the protein antigens hemocyanin, bovine y-globulin, ovalbumin, lysozyme and p-galactosidase were 6to 50-fold lower than AN responses. The defect also decreased secondary IgG2, and IgG3 responses, and primary IgGl and IgGzs responses.The reduced A/WySnJ secondary IgGl response was not due to differential response kinetics or dose responsiveness, and could not be augmented to AIJ levels by repeated immunizations. Serum IgGl, IgG2, and IgG3 levels from nonimmune A/WySnJ mice were similarly reduced. The secondary IgGl response and splenic B cell percentage showed significant positive correlation (Y = 0.72) in F2 mice, suggesting that a single locus controlled both traits. In contrast, A/WySnJ mice made good primary IgM responses to hemocyanin, p-galactosidase, and the thymus-independent antigen trinitrophenyl-Ficoll. The AIWy SnJ splenic adherent cells were competent in antigen-presenting function, and AIWySnJ immune T cells proliferated in response to antigen and provided the requisite B cell stimulatory signals for an IgGl response. Together, our results suggest that AIWy-SnJ mice have a genetic lesion that causes a selective IgG immune response dysfunction. The absence of IgG-secreting cell precursors or a defect in precursor activation or differentiation are two possible mechanisms which could precipitate a selective IgG response dysfunction. We propose that the defective AIWySnJ and normal AIJ strain pair offer the opportunity to use a natural genetic variation as a tool to investigate B lymphocyte development and function.