The Anti-Dextran Response of Scid Mice Transgenic for the Heavy Chain of a Dextran Specific IgM Antibody

Mice homozygous for the scid mutation bear a severe defect in their ability to rearrange V(D)J gene segments to yield active genes for immunoglobulin and T cell receptor molecules. In older animals few clones of B and T cells can arise at random, a phenomenon called leakyness of the scid mutation. We established scid mice carrying as a transgene the rearranged heavy chain of the IgM/λ1antibody MOPC 104E with specificity for the α(1,3) glucosidic linkages in Dextran. Despite the scid defect one-third of these mice immunized with the thymus independent antigen Dextran at 2 weeks of age, and all of those immunized at 6 weeks responded with anti-Dextran antibodies bearing the λ light chain. This indicates that despite the scid mutation these animals had at least once successfully rearranged their endogenous λ1light chain gene segments and harbor Dextran specific B cells. These mice thus provided for the first time the opportunity to study the immune response of B cells of a single specificity in an environment that should, as we shall argue, be devoid of regulatory B and T cells able to recognize the idiotype of the responding cells. One week after immunization the anti-Dextran response of 5- to 6-week-old μ-transgenic scid mice amounted to 30% of the response of μ-transgenic non-scid mice but in essence both responses followed the same kinetics, reaching antibody concentrations indistinguishable from each other 8 weeks after a single dose of Dextran. Furthermore, the ready response of young μ-transgenic scid mice to this antigen by employment of endogenously rearranged λ1light chains allowed experiments to be done to compare the frequency of λ1light chain rearrangements in μ-transgenic scid mice to that in μ-transgenic non-scid mice. This was done in limiting dilution assays counting B cell precursors responsive to mitogen and differentiatingin vitroto produce antibodies toward Dextran. Specific precursors were reduced to about 1% in the spleen of μ-transgenic scid mice when compared to the spleen of μ-transgenic non-scid mice; those in the peritoneal cavity lymphocyte population were reduced to about 12%.