Instruction, Selection, or Tampering with the Odds?

The instruction and selection hypotheses have been variously invoked by opposing camps of immunologists to explain how cells in the immune system know which lineage they are supposed to become. For example, when stimulated by antigen to differentiate, how do T helper cells know whether to become T1 or T2 cells? In their Perspective, Coffman and Reiner discuss new findings that seem to support the selection hypothesis. But they provide an alternative interpretation, proposing that perhaps immune cell differentiation depends on both instruction and selection.