Immune response, tolerance circumvention and autoantibodies in aging MRL/Mp-lpr and MRL/Mp-+ mice.
Isotype distribution was analyzed, as a function of age in MRL/Mp-lpr and MRL/Mp-+ mice. The mice were tested for: (1) "spontaneous" response to nucleic acid (2) induced response to alum-precipitated phosphorylcholine-rabbit gamma globulin (PC-RGG) (immunized animals) and (3) induced response to alum-precipitated PC-RGG after pretreatment with aggregate-free RGG (tolerized-immunized animals). "spontaneous" nucleic acid antibodies of isotypes, other than IgM, increased as animals became older. The quantity of RGG antibody declined as a function of the age at which animals were immunized. Young tolerized-immunized animals made less antibody of all isotypes than did immunized animals. In later life, resistance against tolerance induction developed. Aggregate-free RGG sensitized older animals and, thus, augmented the response to alum-precipitated PC-RGG. Up to the age of 20 weeks, spontaneous antibody and antibody of tolerized-immunized animals showed striking similarities in age- and strain-dependent changes of IgG2b and IgA isotypes. Results were discussed in terms of: (1) a defect in down regulation of immune responsiveness, which contributes to the initiation of autoimmunity and age-dependent resistance to tolerance induction; (2) regulatory mechanisms for isotype switching, which contribute to resistance to tolerance induction, whether naturally occurring or experimentally induced; and (3) age-related immunological changes which are inherent in the MRL/Mp genome, the mutant gene, lpr/lpr, accelerating the changes.
Ponnappan
U
U
Kohno
A
A
Gerber
V
V
Blaser
K
K
Cinader
B
B
D000375:Aging; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D004277:DNA, Single-Stranded / Q000276:immunology; D005260:Female; D007108:Immune Tolerance; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007136:Immunoglobulins / Q000096:biosynthesis*; D051379:Mice; D008815:Mice, Inbred Strains; D010767:Phosphorylcholine / Q000276:immunology; D011817:Rabbits; D005719:gamma-Globulins / Q000276:immunology
D000974:Antibodies, Antinuclear; D004277:DNA, Single-Stranded; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins; D005719:gamma-Globulins; D010767:Phosphorylcholine