Monocyte-Mediated Suppression of Human B Lymphocyte Differentiation in Vitro

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Abstract
Adherent mononuclear cells (AC) from the peripheral blood of myeloma patients and also of healthy individuals in numbers usually present in mononuclear cell (MNC) preparations isolated by the Ficoll-Hypaque method markedly suppress the in vitro plasma cell response of human B cells to PWM. In myeloma patients the mean number of recovered cytoplasmic Ig-positive cells was 4.3 × 103/culture when unfractionated MNC were cultured with PWM and 24.6 × 103 when partially AC-depleted MNC were used. In healthy individuals the mean total number of recovered cytoplasmic Ig-positive cells increased from 19.1 × 103 to 46.2 × 103/culture. Readding partially AC-depleted MNC to plastic adherent cells and also co-cultivation of strongly adherent MNC with partially AC-depleted MNC led to a significant suppression of plasma cell differentiation. Partial depletion of AC not only led to an increased differentiation and proliferation of human B cells but also to a shift in the Ig class distribution of cytoplasmic Ig-positive cells from IgM to IgG. A complete removal of AC, on the other hand, completely abrogated PWM-induced B cell differentiation in vitro. Contrary to the significantly increased B cell proliferation and differentiation after partial depletion of AC, no significant difference could be observed when tritiated thymidine incorporation of unfractionated and AC-depleted MNC after stimulation with PWM or PHA was measured. Adherent mononuclear cells from healthy individuals with suppressor activity for PWM-induced B cell differentiation were shown to be relatively radioresistant. They have to be viable to mediate the suppression; they cannot be removed by depletion of EN-RFC; they are sensitive to carrageenan; and their suppressive activity is not abrogated by treatment with anti-Ia-type serum plus complement under conditions that kill all B cells. These cells therefore were considered to belong to the monocyte/macrophage series.