An Investigation of Methods of Isolation of β2M1 Globulin (Syn.: Iota Protein, 19S γ Globulin, γ1 Macroglobulin, β2M Globulin) and its Association with Isoagglutinin Activity, together with Preliminary Observations on Other Macroglobulins of Slow Electrophoretic Mobility in Normal Human Serum.

An investigation is described of methods of isolation and purification of the high molecular weight protein (here called β2M1 globulin) which us often associated with the isoagglutinin activity of normal human serum. In the course of these experiments it was observed that ultracentrifugal concentration of this protein from serum fractions gives rise to the simultaneous concentration of two other macroglobulins (here called β2M2 and β2M3 globulins). It was found that the concentration of β2M1 globulin in normal serum is about 25-50 mg. per 100 ml. In serum from the blood of normal donors of groups A, B and O, isohaemagglutinin activity is associated with the β2M1-globulin but probably accounts for 1 per cent or less of the total β2M1-globulin concentration in serum. This activity may represent the so-called 'natural' isohaemagglutinin. The immunilogical relation is discussed of the normal β2M1 globulin to certain other members of the 'family' of immune globulins (γ globulin and β2A globulin) and to the pathological macroglobulins occurring in Waldenström's syndrome. Although rabbit antibody to β2M1 globulin cross-reacts with γ globulin, suggesting that a portion of each molecule bears antigenic groupings in common, it was found that a considerable degree of β2M1-globulin specify could be demonstrated after absorbing antisera with purified γ globulin. Attention is also drawn to the evidence that deficiency of either β2M1 globulin or γ globulin can occur independently, suggesting different cellular sources of origin. The pathological macroglobulin demonstrable in Waldernström's syndrome us closely related immunologically to normal β2M1 globulin but is often deficient in isoagglutinin activity. This immunological relation suggests to use of specific anti-β2M1-globulin antiserum as a simple means of distinguishing macroglobulin-aemia from myelomatosis or other conditions with raised levels of γ globulin. The β2M2 and β2M3 globulins are only demonstrable in unltracentrifugal concentrates of normal serum. Evidence is presented to suggest that these proteins are nevertheless present as trace components of normal serum. The solubility and electrophoretic characteristics of these proteins resemble those of β2M1 globulin, but they can be distinguished by immunological methods from β2M1 globulin and each other. Attention is drawn to the evidence that β2M2 and β2M3 globulins may also be increased in the serum of some cases of macroglobulins. [ABSTRACT FROM AUTHOR]