Imbalance in recruitment of IgG (Gm) allotype-producing B-cell subsets from blood to brain in multiple sclerosis

In Gm3/Gm3 homozygous multiple sclerosis (MS) patients, in vitro production of the G1m(3) allotype of IgG1 induced by the T-independent polyclonal B-cell activator Salmonella paratyphi B (SPB) was lower than that of normal individuals of the same Gm phenotype. In contrast, lymphocytes from Gm1/Gm3 heterozygous MS patients responded to the same stimulus with a significantly increased G1m(3) allotype synthesis not observed in normal individuals of the same phenotype. The high level of intrathecal IgG1 production observed in MS patients might be achieved by a selection at the blood-brain barrier of some peripheral T-independent B-cell clones which in Gm3/Gm3 homozygous would bear the G1m(3) allotype, hence a peripheral depletion of this subset, whereas in Gm1/Gm3 heterozygous a preferential admission of the G1m(1)-producing B-cells would lead to a preferential synthesis of this allotype in the central nervous system and to a relative increase of G1m(3) production by the remaining peripheral B cells.