Abnormal selection of antibody repertoires in retrovirus-induced murine AIDS.
The mature B cell repertoire in the course of murine AIDS (MAIDS) was investigated. The polymerase chain reaction (PCR) was used to amplify a large diversity of rearranged Ig H chain genes in normal or infected mice, 2 and 8 wk after virus inoculation. Libraries were constructed from the polymerase chain reaction products. By sequencing V-D-J clones in these libraries and analyzing the respective complementary determining region 3 (CDR3), we have shown at 8 wk the emergence of a population of B cells with significantly less N diversity, some sequences lacking any N addition, a typical feature of fetal repertoires known for degeneracy, and autoreactivities. This decreased N diversity was not present 2 wk after inoculation and could not be related to a defect in terminal deoxytransferase expression because the steady-state levels of terminal deoxytransferase mRNA were found normal in MAIDS bone marrow 8 wk after inoculation. FACS analyses revealed a decreased number of bone marrow B cells (B220+, sIgM+) in MAIDS already present at 2 wk, suggesting an alteration in the pathway of B cell differentiation and resulting in a decrease of peripheral B cells renewal. A relative enrichment of spleen cells in long lived B cells as a consequence of this blockade may participate in the abnormal antibody repertoire selection occurring in MAIDS. These data suggest in the MAIDS pathogeny the relationship between an abnormal repertoire selection and the pathologic process.
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Laboratory of Immunobiology, CNRS URA 359, Institut Pasteur, Paris, France.
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D000818:Animals; D000916:Antibody Diversity; D001402:B-Lymphocytes / Q000502:physiology*; D001483:Base Sequence; D004253:DNA Nucleotidylexotransferase / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D009052:Leukemia Virus, Murine; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016183:Murine Acquired Immunodeficiency Syndrome / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D012333:RNA, Messenger; D004253:DNA Nucleotidylexotransferase