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 <i>xid</i> defect

Abstract

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 T h 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 T h 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 bouyant 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 × BALB/c)F 1 male mice], do not discriminate between the two modes of T h 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% &gt; 65% &gt; 70% &gt; 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 T h cells is not obligatory for B cell activation and does not transfer an essential transmembrane signal to the B cell.

Keywords

Affiliated Institutions

• Howard Hughes Medical Institute US
• Yale University US

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