RAPID BLOOD CLEARANCE OF MOUSE IGG2A AND HUMAN IGG1 IN MANY NUDE AND NU + MOUSE STRAINS IS DUE TO LOW IGG2A SERUM CONCENTRATIONS/

We reported previously that the blood clearance of injected mouse IgG2 a was extremely rapid in many strains of nude and nu/+ mice. In an att empt to determine the cause of this phenomenon, the levels of endogeno us IgG2a in the blood of these mice was assayed. It was found that the serum level of IgG2a was extremely low in many of these mice, below 5 0 mu g/ml, which is 20-100 times lower than the expected normal value. Great heterogeneity between individual mice was observed in their blo od level of IgG2a, and there was an excellent correlation between low blood IgG2a levels and rapid clearance of injected IgG2a. Thus, the bl ood IgG2a levels are so low that a novel, previously undescribed effec t occurs, namely the rapid clearance of small amounts of injected IgG2 a. The clearance is due primarily to binding sites in the spleen and l iver. The low level of endogenous IgG2a is not due to the lack of a th ymus, since it occurs in nu/+ as well as nude mice, but can probably b e attributed to the very clean environment in which these mice are rai sed. In assays of sera from approximately 50 mouse strains, low IgG2a levels were found in an nude colonies and also in some normal mouse st rains. Some nude mice displayed relatively normal IgG2a clearance rate s despite having low levels of endogenous IgG2a. In repeated bleedings of individual mice, IgG2a levels were found to fluctuate greatly. A s imilar clearance effect was observed with a human IgG1 Ab injected int o mice. This rapid clearance of injected IgG, of certain subclasses, r epresents a practical problem for many experiments in which antibodies are used for diagnosis or therapy, and several methods of circumventi ng the problem are discussed.