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Motheaten, an immunodeficient mutant of the mouse. II. Depressed immune competence and elevated serum immunoglobulins
Abstract:
Mice homozygous for the recessive mutation motheaten (me) are deficient in capacity for immune response but show an elevated level of serum immunoglobulins. In comparison to spleen cells from normal sibs, spleen cells from me/me mice have a severely depressed 19S PFC response to SRBC. In the GVH assay, spleen and thymus cells from motheaten donors caused significantly weaker reactions than like cells from normal sibs. Serum electrophoretic patterns of motheaten mice showed increased levels of alpha-, beta-, and gamma-globulins and decreased levels of albumin. Increases in quantities of all major classes of immunoglobulins were found in serum of me/me mice 5 weeks of age and older. Elevation of serum IgM was evident by 3 weeks of age and had reached 25 times the levels in normal sibs by 6 weeks of age. Immunoelectrophoresis and Ouchterlony analysis showed motheaten serum to have both kappa and lambda2 light chains. Evidence of autoimmunity was found in motheaten mice in the granular deposition of IgM and IgG in kidney glomeruli. Motheaten mice, thus, appear to have a severe immune deficiency, but the basic nature of the deficiency is not yet known.
Insights
Motheaten mice exhibit severe immune deficiency despite elevated immunoglobulins. Autoimmunity is indicated by kidney deposition, but the precise immune defect remains unknown.
Area of Science:
- Immunology
- Genetics
- Pathology
Background:
- The motheaten (me) mouse model presents a unique phenotype characterized by immune deficiency and hypergammaglobulinemia.
- Understanding the genetic basis of immune dysregulation in motheaten mice is crucial for deciphering immune system complexities.
Purpose of the Study:
- To investigate the immunological characteristics of motheaten (me/me) mice.
- To explore the underlying causes of immune dysfunction and autoimmunity in this model.
Main Methods:
- Comparative analysis of spleen cell responses (PFC assay, GVH assay) between motheaten and normal mice.
- Serum protein electrophoresis and immunoglobulin quantification.
- Immunoelectrophoresis and Ouchterlony analysis for light chain identification.
- Histopathological examination of kidney glomeruli for immune complex deposition.
Main Results:
- Motheaten mice displayed a severely depressed 19S plaque-forming cell (PFC) response to sheep red blood cells (SRBC) and weaker graft-versus-host (GVH) reactions.
- Serum analysis revealed elevated alpha-, beta-, and gamma-globulins, decreased albumin, and significantly increased levels of all major immunoglobulin classes, particularly IgM.
- Immunoelectrophoresis confirmed the presence of both kappa and lambda2 light chains in motheaten serum.
- Granular deposition of IgM and IgG was observed in kidney glomeruli, suggesting autoimmune processes.
Conclusions:
- Motheaten mice exhibit a profound immune deficiency coupled with hypergammaglobulinemia and evidence of autoimmunity.
- The observed kidney pathology indicates immune complex-mediated damage.
- The fundamental nature of the immune deficiency in motheaten mice requires further investigation.