Common cytokine receptor γ chain (γ(c))-deficient B cells persist in T cell-deficient γ(c)- mice and respond to a T-independent antigen

Abstract

Defects in the common cytokine receptor γ chain (γ(c)) in man result in X-linked severe combined immunodeficiency disease (SCIDX1) characterized by an absence of αβ T cells, γδ T cells and NK cells, with the presence of circulating B cells. Mice made deficient for γ(c) lack γδ T cells and NK cells, but in contrast to SCIDX1 patients have appreciable numbers of αβ T cells, while B cells are reduced about tenfold in numbers and disappear with age. Here we show that when γ(c)- mice are rendered T cell deficient, B cell numbers are still reduced but the age-dependent loss of B cells does not occur. The peripheral B cells which persisted in γ(c)-/nude and γ(c)-/TCRβ(-/-) mice were able to respond to mitogen stimulation in vitro and to mount antigen-specific T-independent lg responses in vivo. These results demonstrate that γ(c)- B cells are functionally competent and suggest that residual αβ T cells are implicated in the B cell loss in γ(c) mice. The γ(c)-/nude and γ(c)-/TCRβ(-/-) mice provide new models to dissect the role of γ(c)-dependent receptors during murine B cell differentiation.