V-region-mediated binding of human Ig by protein A.

The Fab-mediated "alternative" binding of Ig by staphylococcal protein A is a marker of a set of VH genes (a subset of family VH3 in man). We typed 115 monoclonal human Ig as alternative binders or nonbinders. The proportion of binders varied depending on the isotype, 35% in IgM but only 11-13% in IgA1 and IgG3. It was 28% among lambda-chain-bearing but 16% among kappa-bearing monoclonal Ig. Independent estimates of the proportions bound were obtained by studying polyclonal Ig of 10 healthy adults. The proportions bound were close to those observed in the study of monoclonal Ig (the means were IgM 32%, IgA1 13%, IgA2 24%, IgG3 14%). A higher proportion of infant than adult Ig was bound by protein A. Also, the proportion was less isotype-dependent in infants than in adults. At the age of 4 mo, 47% of IgM was bound (mean of 10 children), the values of other isotypes were: IgA1 35%, IgA2 39%, and IgG3 38%. At the age of 14 mo the proportion of alternative binders had decreased but was still far from adult values. We propose that ontogenically early ("virgin") B cells, besides being rich in IgM and lambda-chain producers, are rich in producers of alternative binders. A subsequent selection reduces the proportion of these B cells so that in ontogenically most developed B cell populations, e.g., those producing IgA1 kappa, such cells make up only about 10% of the total.