Essential role of tumor necrosis factor‐α in the differentiation of human tonsil in vivo induced B cells capable of spontaneous and high‐rate immunoglobulin secretion

Abstract

Human tonsils contain B cells capable of spontaneous and high‐rate immunoglobulin (Ig) secretion in vitro. These cells are in vivo induced mature B cells, and, as such, they provide an adequate model for studying tonsil B cell differentiation. The present report analyzes the effect of a variety of factors on purified tonsil B cells capable of spontaneous IgG secretion in fetal calf serum (FCS)‐containing and serum‐free supplemented cultures. Tumor necrosis factor‐(TNF)α was found to be important for these B cells to reach the high‐rate IgG‐secreting stage, as is indicated by the following findings: (a) none of the factors used modified tonsil B cell IgG secretion in FCS‐containing cultures; (b) TNF‐α (5‐20 ng/ml), but not other cytokines or factors including interleukin (IL)‐6, was capable of restoring missing IgG production in serum‐free supplemented cultures of tonsil B cells; and (c) IgG secretion in FCS‐containing cultures was inhibited by the addition of blocking anti‐TNF‐α antibodies, but not anti‐IL‐6 antibodies, and this inhibition could be specifically reversed by exogenous TNF‐α. TNF‐α was actively produced by tonsil B cells (range 120‐750 pg/ml) in the presence, but not in the absence, of FCS. The TNF‐α inductive effect occurred during the first 12 h of culture and did not require DNA synthesis. These results indicate that the early and endogenous generation of TNF‐α seems to be essential for tonsil in vivo induced B cells to differentiate into the high‐rate Ig‐secreting stage.