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

Defects in the common cytokine receptor gamma chain (gamma(c)) in man resul t in X-linked severe combined immunodeficiency disease (SCIDX1) characteriz ed by an absence of alpha beta T cells, gamma delta T cells and NK cells, w ith the presence of circulating B cells. Mice made deficient for gamma(c) l ack gamma delta T cells and NK cells, but in contrast to SCIDX1 patients ha ve appreciable numbers of alpha beta T cells, while B cells are reduced abo ut tenfold in numbers and disappear with age, Here we show that when gamma( 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 cell s which persisted in gamma(c)(-)/nude and gamma(c)(-)/TCR beta(-/-) mice we re able to respond to mitogen stimulation in Vitro and to mount antigen-spe cific T-independent Ig responses in vivo. These results demonstrate that ga mma(c)(-) B cells are functionally competent and suggest that residual alph a beta T cells are implicated in the B cell loss in gamma(c) mice. The gamm a(c)(-)/nude and gamma(c)(-)/TCR beta(-/-) mice provide new models to disse ct the role of gamma(c)-dependent receptors during murine B cell differenti ation.