Programming for recognition and programming for response. Separate developmental subroutines in the murine thymus.
Pre-T cells become programmed with the capacity to make functional responses to activating stimuli in a process that occurs prior to, and independently of, T-cell receptor gene rearrangement and T-cell receptor-dependent positive selection. In spite of this early programming, as differentiation proceeds further the cells enter a stage in which they appear to be unable to make any functional responses. This 'eclipse' phase begins when the cells undergo successful T-cell receptor beta-chain rearrangement and ends, with the return of their functional competence, only when they successfully traverse positive selection. These results suggest that pre-T cells are subject to two distinct subroutines of differentiation, which cannot operate at the same time: one which confers function and one which confers and selects recognition specificity. To provide a possible molecular basis for the relationship between these two processes, we consider specific alterations in response-associated transcription factors that may cause the changes in responsiveness observed during programming for recognition. The interplay of the two differentiation subroutines is proposed to be a consequence of the use of common transcription factors in different combinatorial contexts for functional responses, assembly of T-cell receptor complexes, and selection.
Rothenberg
E V
EV
Division of Biology, California Institute of Technology, Pasadena.
Diamond
R A
RA
Chen
D
D
D000375:Aging / Q000276:immunology*; D000818:Animals; D002454:Cell Differentiation; D015870:Gene Expression; D015322:Gene Rearrangement, B-Lymphocyte; D007376:Interleukin-2 / Q000096:biosynthesis; D051379:Mice; D016513:Mice, SCID; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development / Q000276:immunology*
D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell