Abstract: Antigenic epitopes associated with the extracellular segment of the domain which anchors immunoglobulins to the B cell membrane are disclosed. For IgE, the epitopes are present on IgE-bearing B cells but not basophils or the secreted, soluble form of IgE. The epitope can be exploited for therapy and diagnosis. For example, antibodies or immunotoxins specific for the epitopes associated with the anchor domain of IgE can be used to selectively destroy or downregulate IgE-bearing lymphocytes, thus blocking IgE-mediated allergic reactions. Three different isoforms of the C-terminal segment of the human .epsilon. chain resulting from alternative mRNA splicings in the membrane exon region are disclosed, one of which is secreted and not membrane-bound.