Biphasic Effect of Cyclic AMP on IgG Production and on the Changes of Non-Histone Nuclear Proteins Induced with Anti-Immunoglobulin and Enhancing Soluble Factor

Abstract

The relationship between the changes of non-histone nuclear proteins and the differentiation of B cells to IgG-producing cells was studied by analyzing the effect of exogenously administered dibutyryl cyclic AMP. Stimulation of B cells with anti-Ig or incubation of anti-Ig-stimulated cells with enhancing soluble factor (SF) induced an increase in the amounts and phosphorylation of non-histone nuclear proteins without any concomitant increase or decrease of histones. The addition of 5 × 10^-4 M dibutyryl cyclic AMP or 5 × 10^-5 M isoproterenol at 2 hr after anti-Ig stimulation showed the maximum augmentation of IgG production induced by the sequential stimulation of B cells with anti-Ig and SF. The addition of the same concentration of dibutyryl cyclic AMP within 24 hr after the initiation of the second stage of culture with SF inhibited the induction of IgG. The same biphasic effect of dibutyryl cyclic AMP was observed in the changes of non-histone nuclear proteins induced with anti-Ig or SF. 5 × 10^-4 M dibutyryl cyclic-AMP augmented an increase of amounts or phosphorylation of non-histone nuclear proteins induced with anti-Ig, whereas an increase of amounts or phosphorylation of non-histone nuclear proteins induced with SF was suppressed by the addition of the same concentration of dibutyryl cyclic AMP. The same biphasic effect of dibutyryl cyclic AMP on IgG production and on the changes of non-histone nuclear proteins strongly suggests the intimate involvement of non-histone nuclear proteins in the differentiation process of B cells.