Abnormal regulation of IgG production in multiple sclerosis

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Abstract
After stimulation with pokeweed mitogen (PWM), peripheral blood mononuclear cells (MNC) from patients with active multiple sclerosis (MS) produced significantly more IgG (8595 ng per milliliter, p < 0.01) than MNC from normal age-matched controls (5477 ng per milliliter), whereas those tested during stable periods produced less IgG (4076 ng per milliliter, p < 0.01). Treatment of MNC with sodium periodate (SP) generated suppressor cells for PWM-driven IgG production in normal controls and in most of the stable MS patients but in only 26% of those during active disease, in whom an increase in IgG production was often seen. This suggests a deficiency of inducible suppressor T cells associated with a supernormal B-cell response to polyclonal activation. T lymphocytes obtained from MS patients during active episodes strongly suppressed IgG production by normal B lymphocytes, whereas their B cells often produced more IgG in the presence of normal T cells. In active MS, a relative B-cell unresponsiveness to activated suppressor T cells would leave helper signals unbalanced, thus leading to increased B-cell activation, which might deplete the pool of inducible suppressor cells for IgG production.