Heterogeneity of Antibodies to the Human Blood Groups in Normal and Immune Sera

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Abstract
Summary: The normal antibodies of human sera that are capable of reacting with human B, but not O, red blood cells, are heterogeneous in kind and degree of specificity. These antibody populations are fractionable by absorption with red cells of various animals. Sera from different individuals of group A, for example, contain different relative activities of a β-antibody fraction that will crossreact with opossum red cells and one that will not so cross-react. In certain group O sera, most of the “β antibody” fraction that is not cross-reactive with opossum red cells proves to be absorbable by (and therefore cross-reactive with) human A cells. Inhibition with opossum saliva has effects closely comparable to absorption with opossum red cells. Other fractionations and tests have been performed, using red cells of man, rabbits, guinea pigs, hamsters, cotton rats, Norway rats, chickens, sheep and cattle, singly and in various combinations. In addition to a considerable diversity of normal antibody specificities within particular sera, there are marked differences among the sera of individuals of the same classical blood group, as well as among the different blood groups. Immune sera produced by injecting rabbits with human red cells also display antibody populations with diverse patterns of specificity and cross-reactions. Antibody fractions from different sources, cross-reactive with A and B (but not O) human cells, are not all alike; they vary in other details of their specificities, and are often subfractionable by absorption with related antigens. Experimental data upon which the hypothesis of linkage between specific α and β antibodies has been based are reinterpreted in terms of the heterogeneous antibody populations demonstrated in this study. Fractionation of sera by absorption with animal cells offers promise as a source of reagents for details of antigenic variation in human cells otherwise difficult or impossible to detect. For example, reagents for a pattern of reactivity common to A, B, and certain rare “O” antigens may be obtainable by absorbing selected O sera with particular animal cells. The problem of removing all of the specific α antibodies, but leaving the cross-reactive antibodies, has however not been solved. Other implications of the observations reported in this paper, relevant to the origins and behavior of the normal antibodies, have been discussed.
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