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/lambda1 antibody MOPC 104E with specificity for the alpha(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 lambda light chain. This indicates that despite the scid mutation these animals had at least once successfully rearranged their endogenous lambda1 light 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 mu-transgenic scid mice amounted to 30% of the response of mu-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 mu-transgenic scid mice to this antigen by employment of endogenously rearranged lambda1 light chains allowed experiments to be done to compare the frequency of lambda1 light chain rearrangements in mu-transgenic scid mice to that in mu-transgenic non-scid mice. This was done in limiting dilution assays counting B cell precursors responsive to mitogen and differentiating in vitro to produce antibodies toward Dextran. Specific precursors were reduced to about 1% in the spleen of mu-transgenic scid mice when compared to the spleen of mu-transgenic non-scid mice; those in the peritoneal cavity lymphocyte population were reduced to about 12%.
Nandy
A
A
Fakultät für Biologie, Universität Konstanz, Germany.
Geppert
M
M
Waldschütz
R
R
Lehle
G
G
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D017931:DNA Primers; D003911:Dextrans / Q000276:immunology*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000276:immunology; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology*; D007700:Kinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010537:Peritoneum / Q000166:cytology / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D019076:Transgenes
D017931:DNA Primers; D003911:Dextrans; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains