Expansion of myelopoietic precursors and inhibition of B‐cell precursors in mice that express a T‐cell receptor gamma (Vγ 1.1JγM4Cγ4) transgene

Abstract

Knowledge of the genetic determinants that can affect renewal of multipotential stem cells and their commitment to specific cell lineages is essential to our understanding of multicellular development. However, despite the vast amount of accumulated knowledge in this area, genetic determinants that affect renewal and commitment of precursor cells are unknown. In this study, we demonstrate that three independently derived founder mouse strains, transgenic for the TcR Vγ1.1Jγ4Cγ4 (TcRγ4) chain gene, differed significantly from normal mice in their development of T and B cells as well as myelopoietic precursor cells. Ontogenic programs consistent with an acceleration of T‐cell development and a delayed appearance and suppressed levels of pre‐B‐ and B‐cell precusors were evident in these transgenic mice. In addition, TcRγ4 transgenic mice possessed a significantly elevated level of myelopoietic pluripotent precursors. 3H‐thymidine cell suicide studies suggest that higher percentages of pluipotential precursors from the bone marrow of the TcRγ4 transgenic mice were in the S phase of the cell cycle. These modulations of the lymphoid and myelopoietic compartments, however, were not found in other T‐cell receptor transgenic mice (e.g., TcR Vγ1.2Jγ2Cγ2, TcRγ2; or Vβ8.1Dβjβ2.4Cβ2, TcRβ) constructed with the same or similar cDNA expression vector. The results suggest that the expression of a specific T‐cell receptor γ chain gene, and/or an elevated level of particular subset of TcRγδL cells, may affect the proliferation and relative proportions of haemopoietic and lymphoid precursors. Copyright © 1991 Wiley‐Liss, Inc.