Structure and Function of Murine Immunoglobulin M from Serum and Cell Membrane

Immunoglobulin M (IgM) molecules are secreted into the bloodstream by plasma cells as soluble pentamers and also exist as monomeric integral membrane receptor proteins on the surface of B lymphocytes. Investigation of the structure of membrane and secreted μ chains has provided an understanding of the basis for the existence of IgM molecules in two very different physical environments. The complete amino acid sequence of a μ chain secreted by the murine myeloma MOPC 104E has been determined. When the μ chains of mouse, human and dog are compared, there is a striking gradient of increasing amino acid sequence homology from the NH2-terminus to the COOR-terminus of the μ chain, reflecting a functional conservation of structure. There are five sites of carbohydrate attachment in the mouse μ chain constant region, one of which is present 14 residues from the carboxyterminus. The secreted μ chain (μs) contains no stretches of unchanged amino acids long enough to allow it to exist as an integral membrane protein. IgM molecules synthesized by the murine B lymphoma, WEHI 279, have been characterized. The cells synthesize internal precursors to secreted μ chains which contain incompletely glycosylated complex carbohydrate moieties but in all other respects are identical to secreted μ chains. WEHI 279 membrane IgM is monomeric and contains mature complex carbohydrate structures. The μm and μs chains differ in the structure of their COOR-terminal regions. The carbos hydrate moiety and methionine residue present in the COOR-terminal 19 amino acids of μs chains are absent in μm chains. In addition, four COOR-terminal amino acids which are different from the carboxyterminus of μs chains are released by carboxypeptidase treatment of μm chains. Based on these protein and other nucleic acid data, we believe μm chains possess an uncharged and hydrophobic C-membrane terminal domain which allows monomeric IgM molecules to be integral receptor proteins in the B cell plasma membrane.