The role of B cell surface Ia antigen recognition by T cells in B cell triggering. Analysis of the interaction of cloned helper T cells with normal B cells in differing states of activation and with B cells expressing the xid defect

Abstract

Two discrete mechanisms of T-B cell collaboration appear to exist. In cognate recognition, B cell triggering results from a direct recognition of antigen and MHC determinants at the B cell surface. Alternatively, B cells can be triggered by transstimulation, in which the Th cell is activated by an antigen-presenting cell to produce soluble factors which in turn trigger the B cell. This report addresses the question of whether antigen recognition at the B cell surface in association with Ia determinants delivers a signal to the B cell, which is qualitatively different from the signals delivered by the soluble mediators released by the activated Th cell. Previous reports from a number of laboratories suggest that cognate recognition is obligatory for the triggering of small resting B cells and B cells of the Lyb-5- phenotype, whereas enlarged B cell blasts and the Lyb-5+ subset can be triggered solely by soluble mediators. Contrary to these findings, the experiments described here indicate that B cells isolated in different states of activation from normal spleens on the basis of their buoyant density in Percoll density gradients, or unfractionated B cells from mice differing genetically due to the xid defect [Lyb-5- B cells from (CBA/N X BALB/c)F1 male mice], do not discriminate between the two modes of Th cell function. In both stimulation modes, the high density B cells, and the B cells from xid mice made very poor immunoglobulin secretory responses measured in terms of reverse plaque formation on protein A-coupled erythrocytes. When the responses of different density fractions of B cells were compared under conditions where stimulation occurred either directly or indirectly via transstimulation, the following hierarchy of responsiveness in both the proliferative and plaque-forming cell (PFC) responses was observed in the density fractions 60% greater than 65% greater than 70% greater than 75%. The hierarchy was the same in both modes of interaction and the deficiency of the high density, small B cells was far more marked in the PFC assay than in the proliferative assay. We conclude that the initial proliferative response of the resting B cell can be triggered comparably in vitro under conditions of direct or transstimulation. Thus, recognition of B cell surface Ia by Th cells is not obligatory for B cell activation and does not transfer an essential transmembrane signal to the B cell.