Dendritic cells induce T lymphocytes to release B cell-stimulating factors by an interleukin 2-dependent mechanism.
Dendritic cells (DC) are essential accessory cells for T-dependent antibody responses in culture (1). We have outlined a three-stage mechanism to explain the capacity of DC to stimulate primary antibody responses to heterologous erythrocytes. First, DC induced T cells to produce and to become responsive to interleukin 2 (IL-2). This stage corresponded to the syngeneic mixed leukocyte reaction (2) and involved the clustering of DC and T cells into discrete aggregates. Isolated clusters, representing 5-10% of the culture, were critical for IL-2 release and the production of IL-2-responsive T blasts. In the second stage, IL-2 directly triggered the responsive T cells to release B cell helper factors. This role for IL-2 was documented with a rabbit anti-IL-2 reagent, purified IL-2, and T cells that had been rendered IL-2 responsive by an initial co-culture with DC. T cell growth was not required for IL-2-mediated helper factor release, since irradiated and untreated responders produced similar levels of factor and did so within 3 h of the addition of IL-2. In the final stage, helper factors stimulated the development of antibody-secreting cells from purified B lymphocytes. The helper factors were not H-2 restricted, but for both sheep and horse erythrocytes, the response to factors was antigen dependent and specific. The IL-2 that was present in the DC/T cell-conditioned medium did not act on B cells, since helper activity was neither neutralized nor absorbed by our anti-IL-2 reagent. We conclude that the ability of the DC to induce IL-2 release and responsiveness underlies its capacity to trigger both T and B lymphocyte reactions.
D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D006133:Growth Substances / Q000378:metabolism*; D007376:Interleukin-2 / Q000502:physiology*; D015847:Interleukin-4; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D013154:Spleen / Q000166:cytology* / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism*
D006133:Growth Substances; D007376:Interleukin-2; D015847:Interleukin-4