Fc Receptor-Bearing T Cells and Ig Binding Factors as Class-Specific Suppressors of Polyclonally Activated Human B Cells

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Abstract
By studying the model of polyclonal activation of PBMC from healthy adult humans, selective suppression of the generation of cIgG+ or cIgA+ cells could be achieved by T gamma and T alpha cells activated by Agg-IgG and Agg-IgA, respectively. Furthermore a comparable class-specific suppression was achieved by addition of IgG-BF or IgA-BF released by various cell types including T-enriched PBMC suspensions, B cells or monocytes. The latter effect required the presence of radiosensitive T cells. Whereas T gamma and T alpha cells activated by Agg-Ig inhibited the generation of cIg+ and Ig-secreting cells of the matching class, Ig-BFs were shown to act at a transitional stage of B cell maturation by blocking cIg+ generation and/or proliferation, without impairing Ig secretion by fully differentiated plasma cells. Yet another lectin-like factor, termed BMIF, released by FcR- as well as by FcR+ lymphoid or nonlymphoid cells (e.g. polymorphonuclear neutrophils), could block the maturation of cIg+ into Ig-secreting plasma cells. Unlike Ig-BF, BMIF was not isotype specific. Cells and lymphokines which control the initial stages of B cell activation and differentiation have been extensively investigated but little is known at present about the regulation of the progression from cIg+B blasts to fully differentiated plasma cells. Sequential determination of cIg+ blasts, plasma cells, PFC, and Ig secretion in polyclonally activated PBMC cultures shows an orderly sequence of appearance and decrease of cells at these different stages, suggesting that up and down regulatory signals control each step. Furthermore the demonstration of suppressor pathways which affect B cell maturation at precise transitional stages provides further indirect evidence towards a sequential regulation of each successive differentiation event. In view of the heterogeneity of FcRs with respect to subclass specificity, affinity, cell type distribution and structure, much remains to be done to elucidate the precise regulatory functions of those molecules in the late stages of B cell maturation. From our studies it would appear that some types of Ig-BF would ensure the recognition of Fc determinants on B cell sIg, but still require T cell, and possibly other factors produced by those cells, to alter B cell maturation. This is in keeping with several models in which isotype specific T cells, but not the Ig-BFs thereof, were shown to regulate B cell differentiation.