B cells bind antigen via membrane-bound immunoglobulin (mIg) molecules that are expressed on normal peripheral B cells at 104-10 s copies per cell. mlg molecules differ from secreted antibody molecules in the heavy (H) chain carboxy terminus, which contains spacer, transmembrane and cytoplasmic sequences that are not found in secreted chains 1, 2. Similar sequences are found in the membrane forms of all immunoglobulin H chain isotypes. One of the major unsolved questions regarding these receptors is how they are physically and physiologically coupled to the intracellular molecules, including protein tyrosine kinases and G proteins, that mediate the activation of signal transduction cascades 3-s. Neither mIgM nor mlgD, the predominant membrane immunoglobulins on the surface of mature B cells, have sufficient intracellular structure to provide typical G protein or tyrosine kinase interactive domains: each H chain has a single transmerfibrane-spanning region with a cytoplasmic tail consisting of only three amino acids, KVK6. In view of this limited cytoplasmic structure, it seems most likely that mIgM and mIgD transduce signals via associated proteins.

The amino acid constitution of the 25 amino acid transmembrane-spanning region of the mlgM chain (ixm) suggests that it may contain distinct motifs that can interact with other membrane molecules. This sequence is the most evolutionarily conserved part of the ixm H chain, and is identical in species as distant as human and mouse. Eleven of the 25 amino acids are also shared