Open AccessSuccessive switching of antibody isotypes expressed within the lines of a B-cell clone.
Author(s) -
Patricia J. Gearhart,
Julia L. Hurwitz,
John J. Cebra
Publication year - 1980
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.77.9.5424
Subject(s) - isotype , biology , clone (java method) , antibody , microbiology and biotechnology , immunoglobulin class switching , immunoglobulin heavy chain , b cell , immunoglobulin light chain , phosphorylcholine , j chain , cell culture , gene , immunology , genetics , monoclonal antibody , biochemistry
An antigen-stimulated B cell can differentiate to form a clone of cells that secrete antibodies with the IgM, IgG1, and IgA isotypes. We have examined the sequence of isotype expression by proliferating cell lines within a clone by directly staining for immunoglobulin in the cytoplasm of clonal daughter cells. All of the cones selected for analysis originally secreted IgM as well as other isotypes, as determined by radioimmunoassay of culture fluids. Cell staining showed that (i) at least 25% of the cells contained more than one isotype, indicating that cells can switch expression of isotypes during clonal expansion; (ii) some cells contained both IgM and IgA without detectable IgG1, and some cells contained both IgM and IgG1 without detectable IgA, suggesting that cells can switch from IgM directly to IgG1 or IgA; and (iii) some cells contained both IgG1 and IgA, indicating that cell lines can undergo two successive switches from IgM to the IgG1 and IgA isotypes. Using serological markers for allotypic determinants on the constant region of heavy chains, we have also shown that heterozygous B cells specific for phosphorylcholine generated clones of cells that secreted IgG1 and IgA antibodies that were derived from the expression of genes on only one parental chromosome. Assuming that the gene coding for the IgA isotype is the last gene in the gene cluster coding for heavy chain isotypes, we have proposed a model of successive, but not necessarily stepwise, switching of isotypes within B-cell lines, leading to the eventual accumulation of cells expressing IgA.