To test the hypothesis that gamma 3 is the pivotal isotype for sequential heavy chain switching from mu to each of the gamma isotypes, we have compared the effects of anti-gamma 3 and anti-mu antibodies on the expression of immunoglobulin isotypes in lipopolysaccharide (LPS)-stimulated cultures of mouse spleen cells. IgM-, IgG1-, IgG2b- and IgG2a-containing plasma cells were enumerated by immunofluorescence and secreted immunoglobulins were measured by radioimmunoassay. Although anti-gamma 3 and anti-mu were equally effective in inhibiting the LPS-induced differentiation of IgG3 plasma cells, anti-gamma 3 had no effect on the differentiation of IgM, IgG1, IgG2b, or IgG2a plasma cells. These results support a direct mechanism of heavy chain immunoglobulin switching.
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