Interferon inhibits PWM induced B cell differentiation but not onset of proliferation

The dependence of B lymphocyte differentiation into plasmacytes on anteceding B and T cell proliferation was studied using interferon as a probe. Possible correlations of the effect of interferon on PWM induced T and B cell proliferation and B cell differentiation into either kappa or lambda light chain immunoglobulin synthesizing plasmacytes have been investigated. The hypothesis that the observed inhibition of the PWM induced formation of plasmacytes by interferon is due to putative enhanced suppressor cell activity resulting from increased T cell proliferation is tested. Human, peripheral blood lymphocytes were exposed to PWM in the presence or absence of human leukocyte interferon. Proliferation was assayed by pulse cytophotometric analysis of cell kinetics, as well as [3H]TdR labelling of S-phase cells. Incidence of plasmacytes was detected by immunofluorescence using kappa or lambda light chain specific antibody. During continuous [3H]TdR labelling of stimulated cells, interferon inhibited incorporation of precipitable label by 40% at 96 and 144 h, indicating reduced net DNA synthesis by interferon treated cells. The relative fraction of cells in S-phase as well as G1- and G2 + M- was similar for treated and untreated cells. The fraction of cells rosetting SRBC remained stable for both treated and untreated cells. The size of the interferon treated population was persistently smaller once proliferation began. The time of initiation of proliferation was comparable for treated and untreated cells. Consistent with the findings of others using cell lines, interferon apparently induces a dilation of all cell cycle phases, thereby reducing the rate of proliferation. The same reduction occurred for both T and B cells. Time of initiation of DNA synthesis was, in contrast, not delayed by interferon, suggesting it is specific for events during the proliferative cell cycle. The occurrence of both kappa and lambda light chain immunoglobulin secreting plasmacytes was inhibited by interferon. The degree of inhibition was comparable for both kinds of plasmacytes detected. While not delaying the onset of DNA synthesis, interferon apparently retards subsequent cell proliferation and inhibits the differentiation of B cells to plasmacytes. The data indicate that active cellular proliferation and B cell differentiation require interferon sensitive events which cells initially recruited from quiescence by PWM do not. The inhibition of the incidence of plasmacytes cannot be attributed to an imbalance of T cell proliferation relative to non-T cells.