Successive switching of antibody isotypes expressed within the lines of a B-cell clone.

Publisher Website
Google Scholar
Abstract
An antigen-stimulated B cell can differentiate to form a clone of cells that secrete antibodies with the IgM, IgG1 and IgA isotypes. The sequence of isotype expression by proliferating cell lines [mouse myeloma cells] within a clone was studied by directly staining for Ig in the cytoplasm of clonal daughter cells. All of the clones selected for analysis originally secreted IgM and other isotypes, as determined by radioimmunoassay of culture fluids. Cell staining showed the following: at least 25% of the cells contained more than 1 isotype, indicating that cells can switch expression of isotypes during clonal expansion; some cells contained IgM and IgA without detectable IgG1, and some cells contained IgM and IgG1 without detectable IgA, suggesting that cells can switch from IgM directly to IgG1 or IgA; some cells contained IgG1 and IgA, indicating that cell lines can undergo 2 successive switches from IgM to the IgG1 and IgA isotypes. Using serological markers for allotypic determinants on the constant region of H chains, heterozygous B cells specific for phosphorylcholine were shown to generate clones of cells that secreted IgG1 and IgA antibodies that were derived from the expression of genes on only 1 parental chromosome. Assuming that the gene coding for the IgA isotype is the last gene in the gene cluster coding for H chain isotypes, a model of successive, but not necessarily stepwise, switching of isotypes within B cell lines, leading to the eventual accumulation of cells expressing IgA, was proposed.