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 clone s in these libraries and analyzing the respective complementary determ ining region 3 (CDR3), we have shown at 8 wk the emergence of a popula tion of B cells with significantly less N diversity, some sequences la cking 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 marr ow 8 wk after inoculation. FACS analyses revealed a decreased number o f 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 enr ichment of spleen cells in long lived B cells as a consequence of this blockade may participate in the abnormal antibody repertoire selectio n occurring in MAIDS. These data suggest in the MAIDS pathogeny the re lationship between an abnormal repertoire selection and the pathologic process.