Increased junctional diversity in fetal B cells results in a loss of protective anti-phosphorylcholine antibodies in adult mice.
Fetal Igs are less diverse than adult Igs, largely because of the lack of N addition in the absence of Tdt. To test whether the absence of Tdt is essential, we generated Tg mice that express Tdt and add N regions in fetal B cells. When challenged as adults with PC-containing Streptococcus pneumoniae, these mice fail to make the hallmark T15 anti-PC Ab encoded by canonical rearrangements of Ig H and L chain genes. The anti-PC Abs from these mice are altered by premature N addition and do not protect against death from virulent pneumococcal infection. These results show that maintenance of lower Ig diversity in early life is essential for the acquisition of a complete functional adult repertoire.
Benedict
C L
CL
Department of Microbiology, University of Alabama at Birmingham, 35294-3300, USA.
Kearney
J F
JF
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D000916:Antibody Diversity / Q000187:drug effects; D004253:DNA Nucleotidylexotransferase / Q000096:biosynthesis; D005333:Fetus / Q000166:cytology; D015321:Gene Rearrangement; D015322:Gene Rearrangement, B-Lymphocyte / Q000276:immunology; D014644:Genetic Variation; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010767:Phosphorylcholine / Q000276:immunology*
D000906:Antibodies; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D010767:Phosphorylcholine; D004253:DNA Nucleotidylexotransferase