STRAIN-DEPENDENT LEAKINESS OF MICE WITH SEVERE COMBINED IMMUNE-DEFICIENCY

Mice with immunodeficiency provide an excellent in vivo model for cell transfer experiments. In this study, we compare the extent of immune deficiency of the original CB17 severe combined immune-deficient (SCID ) mice with that of two other strains of immune-deficient mice, the re cently developed C3H SCID mice and the beige/nude/X-linked immune-defi cient (BNX) mice. Detectable levels of serum Ig (higher than 0.4 mug/m l) were found in 79% of CB17 SCID mice studied (n = 24) and in all BNX mice (n = 12); some leaky CB17 SCID mice had normal levels of Ig. in contrast, only 15% of C3H SCID mice (n = 61) had detectable serum Ig; the highest Ig level in this strain was 9.6 mug/ml. Age had no effect on serum Ig concentrations of C3H SCID mice; in contrast, all old (> 1 -year-old) CB17 SCID mice studied had detectable levels of serum Ig. T ransfer of syngeneic, normal, neonatal thymocytes increased serum Ig o f SCID mouse origin to near-normal levels in all CB17 SCID mice but ha d no effect on serum Ig concentrations in C3H SCID mice. Treatment wit h anti-asialo-GM-1 antiserum to abrogate NK cell activity increased se rum Ig levels in 37% of CB17 SCID mice but had no effect on Ig product ion in C3H SCID mice. Flow cytometric analysis failed to identify matu re T or B cells in C3H SCID mice; in contrast, some leaky CB17 SCID mi ce had detectable numbers of T and B cells in the peritoneal cavity. A fter immunization with bacteriophage PHIX 174, neither C3H nor CB17 SC ID mice, including leaky mice, produced specific antibody to phage. In contrast, BNX mice produced small but significant amounts of anti-pha ge antibody. These results indicate that, of the three strains of immu ne-deficient mice, C3H SCID mice have the most severe immune defect. W e predict that C3H SCID mice will be best suited for cell transfer exp eriments.