Natural antibodies to glycans

A wide variety of so-called natural antibodies (nAbs), i.e. immunoglobulins generated by B-1 cells, are directed to glycans. nAbs to glycans can be divided in three groups: 1) conservative nAbs, i.e. practically the same in all healthy donors with respect to their epitope specificity and level in blood; 2) allo-antibodies to blood group antigens; 3) plastic antibodies related to the first or the second group but discussed separately because their level changes considerably during diseases and some temporary conditions, in particular inflammation and pregnancy. Antibodies from the third group proved to be prospective markers of a number of diseases, whereas their unusual level (below or above the norm) is not necessarily the consequence of disease/state. Modern microarrays allowed the determination of the human repertoire, which proved to be unexpectedly broad. It was observed that the content of some nAbs reaches about 0.1% of total immunoglobulins. Immunoglobulins of M class dominate for most nAbs, constituting up to 80-90%. Their affinity (to a monovalent glycan, in K (D) terms) was found to be within the range 10(-4)-10(-6) M. Antibodies to Gal beta 1-3GlcNAc (Le(C)), 4-HSO(3)Gal beta 1-4GalNAc (4'-O-SuLN), Fuc alpha 1-3GlcNAc, Fuc alpha 1-4GlcNAc, GalNAc alpha 1-3Gal (A(di)), Gal alpha 1-4Gal beta 1-4Glc (P-k), Gal alpha 1-4Gal beta 1-4GlcNAc (P-1), GlcNAc alpha-terminated glycans, and hyaluronic acid should be noted among the nAbs revealed and studied during the last decade. At the same time, a kind of taboo is observed for a number of glycans: antibodies to LeX and Le(Y), and almost all gangliosides have not been observed in healthy persons. Many of the revealed nAbs were directed to constrained inner (core) part of glycan, directly adjoined to lipid of cell membrane or protein. The biological function of these nAbs remains unclear; for anti-core antibodies, a role of surveillance on appearance of aberrant, especially cancer, antigens is supposed. The first data related to oncodiagnostics based on quantitation of anti-glycan nAbs are reported.