Antigen presentation by resting B cells. Radiosensitivity of the antigen-presentation function and two distinct pathways of T cell activation.

Abstract

The ability of small resting [mouse] B cells to act as antigen-presenting cells (APC) to antigen-specific MHC[major histocompatibility complex]-restricted T cells as assessed by either T cell proliferation of T cell-dependent B cell stimulation was examined. Ten of 14 in vitro antigen-specific MHC-restricted T cell clones and lines and 3 of 4 T cell hybridomas could be induced to either proliferate or secrete IL-2 in the presence of lightly irradiated (1000 rad) purified B cells and the appropriate foreign antigen. All T cell lines and hybridomas were stimulated to proliferate or make IL-2 [interleukin-2] by macrophage- and dendritic cell-enriched populations and all T cells tested except 1 hybridoma caused B cell activation when stimulated with B cells as APC. Lightly irradiated, highly purified syngeneic B cells were as potent a source of APC for inducing B cell activation as were low density dendritic and macrophage-enriched cells. Lymph node T cells freshly taken from antigen-primed animals were also found to proliferate when cultured with purified B cells and the appropriate antigen. Thus, small resting B cells can function as APC to a variety of T cells. This APC function was easily measured when the cells were irradiated with 1000 rad but was greatly diminished or absent when they were irradiated with 3300 rad. Thus, the failure of some other laboratories to observe this phenomenon may be the result of the relative radiosensitivity of the antigen-presenting function of the B cells. This radiosensitivity allowed easy distinction of B cell antigen presentation from presentation by the dendritic cell and macrophage, as the latter was resistant to 3300 rad. One T cell clone that failed to proliferate when B cells were used as APC was able to recruit allogeneic B cells to proliferate in the presence of syngeneic B cells and the appropriate antigen. Evidently, there are at least 2 distinct pathways of activation in T cells, 1 that leads to T cell proliferation and 1 that leads to the secretion of B cell recruitment factor(s).