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By Frank J. Dixon, K. Frank Austen, Leroy E. Hood, Jonathan W. Uhr (Eds.)

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A model incorporating these findings is shown in Fig. 9. The results suggest that there are two pathways of B cell activation. One pathway requires T cell influences from initial triggering to allow subsequent maximal proliferation and differentiation in response to IL-2. The alternative pathway in which B cells are activated in the absence of T cell influences, subsequently requires a growth and differentiation promoting activity(~)within T cell supernatant that is distinct from IL-2. , the activities that support the growth of activated B cells.

The early requirement for T cell influences to promote maximal IL%driven B cell responses could have many explanations. Although T cell influences are not required for the expression of IL-2 receptors, they may be necessary for B cells to express high-avidity IL-2 receptors. Recent work by Prakash et al. (1985) has indicated that highaffinity IL-2 receptors were induced on murine B cells only when stimulated by both anti-Ig and T cell-derived helper factors. If human B cell responses to IL-2 require high-affinity IL-2 receptors and the induction of high-affinity IL-2 receptors requires T cell lymphokines, then proliferation and differentiation of B cells in response to IL-2 would be anticipated to require the presence of T cell influences during initial activation.

In an effort to determine whether the T cell signals that enhanced subsequent B cell differentiation were delivered before or after cell division, experiments utilizing hydroxyurea were undertaken. 2 ~~ 1 36hr 2 48 hr SA SA SA SA + T supt + T supt 96 hr 96 hr From Jelinek and Lipsky (1985). B cells were cultured with SA or SA + mitogen-activated T cell supernatant (T supt) for varying lengths of time before being washed and recultured in the second incubation. B cells were cultured in the presence of fresh T cell supernatant for varying lengths of time prior to assay for total number of Ig-secreting cells (ISC).

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