Severe immunodeficiency has opposite effects on neuronal survival in glutamate-susceptible and -resistant mice: adverse effect of B cells.
The resistance of rats or mice to glutamate-induced toxicity depends on their ability to spontaneously manifest a T cell-dependent response to the insult. Survival of retinal ganglion cells (RGCs) exposed to glutamate in BALB/c SCID mice (a strain relatively resistant to glutamate toxicity) was significantly worse than in the wild type. In the susceptible C57BL/6J mouse strain, however, significantly more RGCs survived among SCID mutants than in the matched wild type. RGC survival in the SCID mutants of the two strains was similar. These results suggest 1) that immunodeficiency might be an advantage in strains incapable of spontaneously manifesting protective T cell-dependent immunity and 2) that B cells might be destructive in such cases. After exposure of RGCs to toxic glutamate concentrations in three variants of B cell-deficient C57BL/6J mice, namely muMT(-/-) (B cell knockout mice) and Ii(-/-) mice reconstituted with transgenically expressed low levels of Ii p31 isoforms (p31 mice) or Ii p41 isoforms (p41 mice), significantly more RGCs survived in these mice than in the wild type. The improved survival was diminished by replenishment of the B cell-deficient mice with B cells derived from the wild type. It thus seems that B cells have an adverse effect on neuronal recovery after injury, at least in a strain that is unable to spontaneously manifest a T cell-dependent protective mechanism. These findings have clear implications for the design of immune-based therapies for CNS injury.
Schori
Hadas
H
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
Lantner
Frida
F
Shachar
Idit
I
Schwartz
Michal
M
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease; D018698:Glutamic Acid / Q000008:administration & dosage / Q000633:toxicity*; D007113:Immunity, Innate / Q000235:genetics; D007267:Injections; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D009474:Neurons / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D013045:Species Specificity; D014822:Vitreous Body
D018698:Glutamic Acid