Anti-gamma globulin antibodies in the rabbit. Titer variations after autologous gamma globulin injection

Abstract

Evolution of the Titer of Anti-Gamma Globulin Antibodies in the Rabbit. After Injection of Antologous Gamma Globulin

The normal existecen of anti gamma globulin antibodies has been described in several animal species, including man.

In a series of ten rabbits we found an average value of 1:3.2, as determined by an agglutination technique using charcoal particles as inert material. Following this baseline determination, the rabbits were bled at intervals and gamma globulin from each animal was obtained by means of Na2S2O3 precipitation. After a rest period (30 to 60 days) and upon the recovery of normal plasma protein values, each ani­ mal was injected with its own gamma glo­ bulin, dissolved in 20 mi of saline. The amount injected varied between 0.30 and 0.41 g.

Twelve hours after the injection, the plasma protein values showed a decrease from 55.9 to 50 g%o» with a decrease from 36.3 to 31.2 g °/00 in the albumin fraction. This could be expected in view of the 10 percent increase in the plasma volumen produced by the injection of a gamma globulin solution. Remarkably, no changes were observed in the gamma globulin levels. It can be assumed that a true increase in the amount of circulating gamma globulin had taken place, this in­ crease being counterbalanced by the accompanying hemodilution (fig. 1). Twenty four hours after the injection, the valúes of total protein and albumin showed a trend towards normalization (probably due to a fluid equilibration involving the extravascular space). This trend was, however transient the recovery being really initiated by the 5th day post-injection.

Between the first and second day after injection, a slight decrease (from 8.9 to 6.5 %o) was observed in the gamma glo­ bulin valúes (p < 0.05). Concomitantly, there was a sudden fall in the titer of anti gamma globulin levels. From the sixth 1:0.3; p<0.01, and to zero and 1:0.3, 24 and 48 hours after the injection; p<0.005andp<0.01respectively).This coincided with a slight decrease in the gamma globulin levels. From the sixth day on, after the injection, a slow but con­sistent increase in the titer of antibodies took place. Seventeen days after the in­jection the titer was clearly higher than originally: 1:7.3 (p < 0.05).

The existence of anti gamma globulin antibodies in the normal rabbit is verified. Their quick disappearance after the administration of a considerable dose of auto gamma globulin to the animal may be explained on the basis of the formation of antigen-antibody complexes, rapidly removed from the circulation. This interpretation is strengthened by the observed simultaneous decrease (significant though slight) of plasma gamma globulin. The presence of anti gamma globulin antibo­dies, as well as the remarkable increase over the initial value, as shown in this study, may be explained by the existence of an antigen-dependent homeostasis, an immunologic equilibrium between persistent antigenic stimulus and antibody response, as postulated by one of us (Gras).

Previous experiments have shown that a persistent antigenic stimulation at a constant level produces an inhibition of antibody formation; this inhibition being established at low or zero level of circu­lating antibodies. In these conditions of inhibition, the animal is still able to respond to a sudden increase in the dose of the antigenic stimulus. These experiments led to the postulation of the existence of an immunologic equilibrium between an­tigenic stimulus and antibody response, since this equilibrium is reached specifically for the antigen in a situation of per­ sistent stimulus at a constant level, ends when this persisten stimulus ceases, and it is broken by a change in stimulus intensity. Thus, this equilibrium does not show the features of the States of antibody-dependent immunologic homeostasis or of non response by exhaustion of antigen-sensitive cell. It must be, therefore, an antigen-dependent state of immunologic homeostasis.
Circulating antigens, like plasma proteins and those of erithrocytes, platelets and leukocytes (in which are found anti­ gens of histocompatibility) stimulate the immunocompetent cell system in a persis­tent manner at a very constant level since the embryonic or perinatal period. Thus, the organism is, as far as they are con­cerned, in this state of immunologic homeostasis, habitually at a zero level of circulating antibody (or in some cases at a low level). An example of this situation can be found in the normal coid agglutinins. These are anti antigen I autoantibodies and in normal individuals they are found intiters around 1:2. The antigen I presents the peculiarity of maturing in the postnatal period, contrary to the other he­matic antigens. This study could provide a similar example. The changes in the titer after administering a considerable quantity of auto gamma globulin would be explained as resulting from the formation of antigen-antibody complexes (phase of decrease in the titer) and the establishment of an immunologic equilibrium at a higher level than initially (consecutivo to a sudden increase in antigenic stimulus). It may be logically assumed that the titer will return afterwards to the initial levels (as suggested by Fig. 1).

The observed changes further support the existence of an immunologic equili­brium between persistent antigenic stimulus and antibody response.