B cells use immunoglobulin M (IgM) and IgD as antigen receptors, but after contact with antigen they can switch and use IgG, IgA, or IgE. In mice lacking the transmembrane and cytoplasmic domains of IgE, serum IgE is reduced by more than 95 percent and, after immunization, specific responses are negligible. In mice lacking most of the cytoplasmic tail of IgE, serum IgE levels are reduced by 50 percent and specific responses are reduced by 40 to 80 percent, without a clear secondary response. Thus, membrane expression is indispensable for IgE secretion in vivo, and the cytoplasmic tail influences the degree and quality of the response.