Common cytokine receptor gamma chain (gammac)-deficient B cells persist in T cell-deficient gammac-mice and respond to a T-independent antigen.
Defects in the common cytokine receptor gamma chain (gammac) in man result in X-linked severe combined immunodeficiency disease (SCIDX1) characterized by an absence of alphabeta T cells, gammadelta T cells and NK cells, with the presence of circulating B cells. Mice made deficient for gammac lack gammadelta T cells and NK cells, but in contrast to SCIDX1 patients have appreciable numbers of alphabeta T cells, while B cells are reduced about tenfold in numbers and disappear with age. Here we show that when gammac- 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 gammac-/ nude and gammac-/TCRbeta-/- mice were able to respond to mitogen stimulation in vitro and to mount antigen-specific T-independent Ig responses in vivo. These results demonstrate that gammac- B cells are functionally competent and suggest that residual alphabeta T cells are implicated in the B cell loss in gammac mice. The gammac-/nude and gammac-/TCRbeta-/- mice provide new models to dissect the role of gammac-dependent receptors during murine B cell differentiation.
Vosshenrich
C A
CA
Institute for Genetics, Cologne, Germany.
Sharara
L I
LI
Guy-Grand
D
D
Rajewsky
K
K
Müller
W
W
Di Santo
J P
JP
D000818:Animals; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D018121:Receptors, Cytokine / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018121:Receptors, Cytokine