Contact Between Good Friends: What Limiting Dilution Analysis Taught Us

The demonstration in the 1960s that T cells collaborated with B cells in enabling antibody responses to simple protein antigens opened up the challenge of how to investigate the interactions of two rare antigen‐specific lymphocytes within a vast population. One idea was that T cells made soluble factors that could activate B cells at a distance; the other was that rare T cells and B cells came into contact. Using limiting dilution analysis, we asked the question ‘How many B cells could a single T cell collaborate with in the short term?’ Unequivocally, the answer was just one. This implied a need for cell contact, and coupled with the observation for genetic restriction in T‐cell/B‐cell co‐operation, seemed to make a watertight case for direct coupling. Claims of diffusible antigen‐specific factors undermined the importance of our findings at that time. Remarkably, those claims have not yet been retracted and our original findings that collaborating T cells and B cells must come into contact have never achieved the recognition that they deserved.