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

Citation

Kehry, Marilyn Rose (1980) Structure and Function of Murine Immunoglobulin M from Serum and Cell Membrane. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/nyc2-gv40. https://resolver.caltech.edu/CaltechTHESIS:07232025-144534720

Abstract

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 (μ_s) 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 μ_m and μ_s 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 μ_s chains are absent in μ_m chains. In addition, four COOR-terminal amino acids which are different from the carboxyterminus of μ_s chains are released by carboxypeptidase treatment of μ_m chains. Based on these protein and other nucleic acid data, we believe μ_m 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.

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