Mannan binding lectin and its interaction with immunoglobulins in health and in disease.
In humans there are five classes of immunoglobulins (Igs), IgG, IgM, IgA, IgE and IgD, all of which are glycoproteins. The Igs are the major secretory product of the adaptive immune system, and they bind to antigens via variable sequences on their Fab regions. The binding to antigen results in neutralization or agglutination of bound material and also initiates effector functions via the Fc regions, such as opsonisation and activation of the classical complement pathway through binding of C1q. Mannan binding lectin (MBL), the 'recognition' molecule of the lectin pathway of complement activation, is homologous in structure to C1q, and binds in a calcium-dependent manner to terminal mannose and GlcNAc residues which have been identified on the oligosaccharides N-linked to the Igs. MBL binds agalactosylated glycoforms of IgG (IgG-G0), polymeric forms of IgA and certain glycoforms of IgM which have a high incidence of GlcNAc-terminating glycans. This interaction provides a route of clearance of immune complexes from the serum, and a mechanism of complement activation to Ig-coated pathogens. In disease, MBL contributes to inflammation in Rheumatoid Arthritis, a condition in which serum IgG-G0 concentrations can increase significantly compared to healthy individuals. MBL has recently been demonstrated to bind Ig in the B cell receptor complex which expresses abnormal variable region glycosylation, in follicular lymphoma.
Arnold
James N
JN
Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom. james.arnold@bioch.ox.ac.uk <james.arnold@bioch.ox.ac.uk>
Dwek
Raymond A
RA
Rudd
Pauline M
PM
Sim
Robert B
RB
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D003167:Complement Activation / Q000276:immunology*; D015922:Complement C1q / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology*; D006031:Glycosylation; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology*; D037601:Mannose-Binding Lectin / Q000276:immunology*; D009844:Oligosaccharides / Q000276:immunology
D006023:Glycoproteins; D007136:Immunoglobulins; D037601:Mannose-Binding Lectin; D009844:Oligosaccharides; D015922:Complement C1q