Evidence for a C-terminal tyrosine residue in human and mouse B-lymphocyte membrane μ chains

Abstract

THE antigen receptor on the plasma membrane of both human and murine bone marrow-derived (B) lymphocytes has been shown to be mainly monomeric IgM (refs 1–5), but the mechanism of attachment of this IgM is not known. Studies on other membrane proteins (for example, glycophorin⁶, cytochrome b₅, (ref. 7) and probably HLA⁸) have shown that they are bound to the membrane by means of a hydrophobic polypeptide stretch in the C-terminal region, but secreted IgM heavy chains terminate in an extra-domain sequence of 19 amino acid residues^9–11, which is not sufficiently hydrophobic to act as an integral membrane component. Membrane μ chains, however, might carry a further hydrophobic C-terminal polypeptide section instead of, or in addition to, the C-terminal stretch present in secreted μ chains. To investigate this possibility, we have exploited the fact that a tyrosine residue forms the C terminus of all examined secreted μ chains, including those of human and mouse. Since it is improbable that a hydrophobic extension on the membrane μ chain would coincidentally carry a C-terminal tyrosine residue, we have examined the surface IgM from a murine B lymphocytoma, McPc 1748 (ref. 12), and a human lymphocytic B-cell line, Bristol-8 (Bri-8, obtained from G. D. Searle, High Wycombe), which also carries surface IgM (F. Kramer, personal communication), to see whether a C-terminal tyrosine residue can be cleaved from their purified μ chains by treatment with carboxypeptidase. Our data show that it can, indicating that membrane-bound IgM lacks an extra hydrophobic piece.