IN VITRO ANALYSIS OF ANTIBODY REGULATION IN HUMANS

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Human lymphoblastoid B cells are a subset of highly activated B cells which are induced by in vivo immunization. In vitro these B cells produce antibody without the need for T-cell help or mitogen stimulation, and the majority of the antibody production is complete by day 3 of culture. In the past year, we found that the antibody-producing capacity of these cells can be reduced in vitro by NK cells and a separate suppressor T-cell subset. In the coming year, we will determine whether all NK cells have this inhibitory capacity or, as suggested by our earlier studies, only a subset of NK cells performs this function. We will test this by selective removal and/or isolation of different subsets of NK cells using monoclonal antibodies with differing specificities. We have recently determined that the two suppressor cells recognize different target structures on the B cell, with the NK cell recognizing the transferrin receptor and the T cell recognizing a separate, as yet undefined structure. It is also clear from our studies that not all lymphoblastoid B cells are capable of being inhibited. Although the two suppressor cells recognize different target structures, they appear to recognize the same B-cell subsets. This B-cell stage appears to be a proliferating cell which has not yet developed the capacity for antibody secretion. (LB)