PRODUCTION OF a RUNTING SYNDROME AND SELECTIVE ΓA DEFICIENCY IN MICE BY THE ADMINISTRATION OF ANTI-HEAVY CHAIN ANTISERA

Abstract

Conventional Swiss mice were treated from birth with intraperitoneal injections of anti-immunoglobulins in an attempt to create an experimental dysgammaglobulinemia. Mice treated with anti-γM were immunologically suppressed in all immunoglobulin classes as determined by serum antibody titers, splenic plaque-forming cells, serum immunoglobulin levels, and immunofluorescent analysis of plasma cells in lymphoid tissues. Treatment immediately after birth with high concentrations of anti-γM leads to a developmental arrest characterized by severe immunosuppression, failure to gain weight, and premature death. The pathogenesis of anti-γM runting syndrome is unknown. Animals similarly treated with anti-γG, anti-γA, or control normal goat or rabbit γ-globulins developed normally. The frequency of occurrence and severity of anti-γM-induced runting syndrome is dependent upon the concentration of anti-γM-globulin administered. Administration of anti-γA resulted in a selective γA deficiency that was characterized by a marked reduction in serum-γA and an absence of γA-containing cells in the spleen. However, essentially normal numbers of plasma cells were found in the gastrointestinal lamina propria of anti-γA-treated animals concomitantly with suppressed levels of γA in intestinal fluids.

The effect of anti-mu suppression of gammaM and gammaG on the production of gammaE.

“…While all studies agree on the potent immunosuppressive ability of anti-mu chain sera, experiments using anti-~ chain sera in nongerm-free states have not demonstrated an equally potent suppressor effect (20,21,23). The reason for this is not certain, but at least in vivo is probably related to the large amounts of maternal ~/G present in the circulation of newborn mice which may result in rapid removal of administered anti-),G before it can act at a cellular level (24). It is this maternally derived ~/G that explains the inability of anti~M to eliminate serum ~G~ and ~G2.…”

“…The fact that anti-mu chain sera is completely suppressive in these experiments while anti~ chain sera is less potent could be explained if the affinity of~/G receptors for antigen is greater than that of~M receptors. It is well established that treatment with anti~A affects only ~A production (22,24). Thus, for the three major immunoglobulin classes, a ~M to ~/G to ~/A sequence or a selective ~/M to ~G to ~/M development remain viable alternatives.…”

Antibodies to Human Albumin in Cirrhotic Sera

“…The antibody could alter the synthesis and/or catabolism of albumin. There is precedence for an effect of antibody on both synthesis (20) and catabolism (21) of proteins. It is also conceivable that immune complexes containing altered albumin or the development of delayed hypersensitivity to albumin might perpetuate liver damage initiated by alcohol.…”

Evidence for an immunoglobulin-dependent antigen-specific helper T cell.

“…In the second, conventionally raised mice were used and were treated with goat anti-M chain globulin (18). In the third experiment, CBA/H mice were injected from birth with rabbit anti-c chain serum according to Murgita et al (16). The mice were immunized at 6 weeks of age and tested 1 week later.…”