In vivo analysis of the cytoplasmic domain of mIgE antibodies.

All immunoglobulin molecules exist in two forms, one integrated into the plasma membrane and displayed on the cell surface as the B cell receptor [1], the other secreted into tissue fluids as the soluble antibodies. Any given B lymphocyte has the potential of producing both forms. The membrane-bound form and the secreted form produced by a single B cell have identical light chains and identical heavy chains except for a short segment at the C terminus. This segment consists of a 'spacer' sequence, followed by a stretch of hydrophobic amino acids (transmembrane region) and the cytoplasmic region which differs in size between the Ig classes. Little is known about the function of intracellular tails of IgG, IgA and IgE. They differ from those of IgM and IgD, which have only three intracellular amino acids (Lys Val Lys). The intracellular parts of IgG, IgA and IgE are longer. Using a gene targeting technique by homologous recombination in ES cells [2, 3], combined with the prokaryotic CRE-recombinase system [4], we constructed two mice. One with the membrane exons and a mutated cytoplasmic tail in place (KVKdelta tail), and one with essentially only the sequence coding for the secreted form of IgE (delta M1M2). Measurements of the steady-state level of IgE showed that in delta M1M2 mice IgE can only be detected at a minimal level, whereas in KVKdelta tail mice serum IgE is reduced by about 50%. These data allow us to speculate about a specific function of the cytoplasmic tail of mIgE antibodies. We think that the cytoplasmic tail of IgE is involved in signal transduction which leads to the expression of high quantities of secreted IgE.