Fig. 4

A hypothesis on the origin of antibodies against self glycans in patients with neurological disorders. Within the B cell repertoire able to respond against non-self glycans exist cell populations that recognize glycan molecules structurally related to self glycans. Although these so-called “treacherous” B cells cannot be stimulated by self glycans, during their activation by non-self structures they can undergo mutations that reshape the binding site, with some changes now leading to self glycans recognition (drift). These “drifted” B cells can then be activated by self glycans inducing the production of IgM antibodies (and IgG ones, if isotype switch occurs). Thus, these actions lead to a concordant anti-self glycan IgG/IgM antibody response. Alternatively, non-self glycan-stimulated “treacherous” B cell can switch their isotype to become “treacherous switched” B cells, producing anti-non-self glycan IgG antibodies. Subsequent drift events can now generate “drifted and switched” B cells that produce IgG after stimulation with self glycans. These latter steps can generate a discordant anti-self glycan IgG antibody response (i.e. without IgM antibodies)