Studies on the capacity of B cells to serve as antigen-presenting cells.

Abstract

Abstract In this paper we have tested the hypothesis that B cells, via their Ig receptors, can take up, process, and present antigen to T cells in an analogous manner to macrophages. Rabbit IgG (NRGG) was used to immunize mice for an antigen-specific proliferative response. Rabbit anti-mouse Ig (RAMIG), a test antigen that could bind to all B cells via their membrane Ig, and NRGG, an antigen that would bind to only a very few antigen-specific B cells, were compared for their capacity to stimulate a T cell proliferative response when macrophages or B cells, in the form of macrophage-depleted spleen cells (MDSC), were used as the source of antigen-presenting cells. When macrophages were used as antigen-presenting cells, NRGG and RAMIG were indistinguishable in their capacity to stimulate a proliferative response in NRGG-primed T cells. In contrast, when MDSC were used as a source of antigen-presenting B cells, only RAMIG, and not NRGG, stimulated T cell proliferation. That the T cells, also present in the MDSC, were not involved in the antigen presentation was demonstrated by the fact that treatment of MDSC with anti-Thy 1 and complement did not decrease the capacity of RAMIG-pulsed MDSC to stimulate a proliferative response. A variety of experiments were carried out in an attempt to rule out the possibility that contaminating macrophages might have been responsible for these results. The fact that NRGG-pulsed MDSC did not induce proliferation indicated that insufficient macrophages were present in the MDSC to account for the proliferative response by a mechanism involving the direct uptake of antigen by such contaminating cells. The inability of MDSC to present another antigen, ovalbumin, in a similar T cell proliferative response strengthens that conclusion. The possibility that the immune complexes formed between RAMIG and B cell Ig created a “super antigen” that could be taken up very efficiently by a small number of contaminating macrophages was also investigated. The evidence against this possibility was: 1) Heat-aggregated NRGG did not stimulate a proliferative response when MDSC were used as presenting cells. 2) If after being pulsed with RAMIG the MDSC were inactivated by freeze-thawing or ultraviolet irradiation, no proliferative response was induced. Furthermore, the presentation of RAMIG by MDSC was shown to be genetically restricted in that T cells incorporated 10- to 30-fold more 3H-thymidine when presented antigen by syngeneic compared with allogeneic RAMIG-pulsed MDSC. We concluded from these experiments that under the experimental conditions employed, B cells were capable of directly presenting antigen to T ceils in a genetically restricted fashion. If correct, this could represent a mechanism by which antigen-specific T-B interaction takes place.