FACTORS CONTROLLING SERUM Γ-Globulin CONCENTRATION

Abstract

The mechanisms which regulate the serum level of T-globulin (or other serum proteins) are poorly understood, although a balance between the rate of production (synthesis) and rate of removal (catabolism) must exist for the maintenance of a constant serum level. T-Globulin synthesis has been demonstrated in plasmacytes and related cells of the spleen, lymph node, bone marrow, and other tissues following antigenic stimulation (1-3), and the turnover of T-globulin has been determined by means of radioisotopically labeled protein. The anatomic and cellular sites of degradation are still unknown, however, and the mechanisms regulating the rate of T-globulin catabolism are poorly understood.Several observations indicate that the rate of ~,-globulin catabolism may be related to the serum T-globulin level. T-Globulin catabolism is generally accelerated in patients with increased T-globulin levels due to inflammatory diseases (4-9) or plasma cell malignancy (7-11). Similarly in mice with plasma cell tumors and large amounts of T myeloma proteins, T-globulin catabolism is accelerated (12). Conversely, prolonged T-globulin survival has been found when the serum T-globulin level is low (9,11,13,14). Two variable factors, however, were present in these studies; i.e., the amount of serum gamma globulin and the number of plasma cells. Patients with low T-globulin levels had reduced numbers of plasma cells, and patients with large amounts of ~-globulin had increased numbers of plasma cells. Soons and Westenbrink (15), on the basis of isotopically labeled protein studies, obtained some evidence that plasma cells might be the site of T-globulin destruction. If this is the case, then T-globulin catabolism would be increased when the number of plasma cells is increased and decreased with plasma cell reduction. Because of the uncertainty about the roles of the plasma cells and the serum gamma globulin level, the present studies were undertaken to clarify the factors determining the rate of T-globulin catabolism. Inbred BALB/c mice were used (a) to reduce genetic variability to a minimum, (b) because fl, A-globulins as well as ~,-globulins from BALB/c mice were available in large quantities, (c) because transplantable * Work done as

The Immunoglobulins of Mice

“…This similarity indicated that catabolism was regulated by a property common to these classes of immunoglobulin. Other studies have shown that this is a property of the heavy polypeptide chain of the molecule (5).…”

“…3,1A-globulin catabolism was also unaltered by the presence of large amounts of "),lA-myeloma protein (Table II). (5,16,17) have shown that the administration of human 7S v-globulin to mice accelerates the catabolism of normal 7S v-globulin of mouse origin. The effect of human 7S v-globulin on each of the mouse 7S v-globulin components was investigated in the present work.…”

“…Prior studies of the turnover of Ira-labeled normal 7S immunoglobulins have shown a progressive change (flattening) of the decay curve; i.e., a progressive reduction in the fractional rate of catabolism of the labeled protein (5,16). This finding could be accounted for by the existence of molecules with different catabolic properties in the normal population.…”

“…The finding of normal 7S immunoglobulin half-lives of about 4 days in normal mice and 10 days in low pathogen mice (5,16) indicate that the short-lived 7S ~'2b-molecules may represent only a small part and ~,~-and 7S 5'l-globulin molecules a larger part of the normal IgG (7S "r-globulin) population.…”

“…Differences in the catabolic control of immunoglobulins are also discernable. The serum level of 7S 7-globulin (IgG) helps to determine the catabolic rate; the higher the serum level, the greater the catabolic rate (5,6). 18S 71-macroglobulin (IgM) catabolism, however, appears to be unrelated to the serum 71-macroglobulin level (2).…”