BLOCKADE OF T-LYMPHOCYTE AND B-LYMPHOCYTE DEVELOPMENT BY ANTIBODY TO THE GAMMA(C) SUBUNIT OF THE RECEPTORS FOR INTERLEUKIN-2, INTERLEUKIN-4, AND INTERLEUKIN-7

Cytokines are important regulators of hematopoesis. Mutations in gamma (c), which is a subunit shared by the receptors for interleukin (IL) 2 , IL-4, and IL-7, have been causally associated with human X chromosom e-linked severe combined immunodeficiency disease, This finding indica tes a mandatory role for cytokine receptor signaling at one or more st ages of lymphocyte development. To evaluate the cellular level at whic h gamma(c) is critical for lymphopoiesis, the effect of monoclonal ant ibodies to gamma(c) on the capacity of syngeneic bone marrow cells to reconstitute the hematopoietic compartment of lethally irradiated reci pient mice was examined, We show that monoclonal antibody to gamma(c) blocked lymphocyte development at or before the appearance of pro-B ce lls and prior to or at the seeding of the thymus by precursor cells wh ite erythromyeloid cell development was normal, These results suggest that one level of lymphocyte development that requires gamma(c) is a p oint in hematopoietic cell differentiation near the divergence of lymp hopoiesis and erythromyelopoesis.