IN-VIVO AND IN-VITRO IGE ISOTYPE SWITCHING IN HUMAN B-LYMPHOCYTES - EVIDENCE FOR A PREDOMINANTLY DIRECT IGM TO IGE CLASS SWITCH PROGRAM

Molecular analysis of circular excision products and composite genomic switch regions has demonstrated that in mice, immunoglobulin (Ig) iso type switching from IgM to IEE often proceeds sequentially via IgG1. B ased on analysis of Ig production in cell cultures, it has been sugges ted that human B cells may switch to IgE via IgG4, whereas limited mol ecular data from in vitro switched B cells suggest a direct IgM to IgE switch program. To obtain a quantitative assessment of direct versus sequential IgE switching in humans,we have analyzed the nucleotide seq uences of 29 composite S mu/S epsilon switch regions from freshly isol ated human B lymphocytes from patients with atopic dermatitis and from B lymphocytes induced to switch to IgE synthesis in vitro. The data s how that in these B cells IgE isotype switching progressed directly fr om IgM to IgE. We conclude that, in contrast to the murine IgM/IgE swi tch program, the IgM to IgE switch in B lymphocytes from patients with atopic dermatitis as well as in vitro stimulated B cells from healthy donors preferentially proceeds via direct S mu to S epsilon switch re combination.