ENDOGENOUS VH GENE FAMILY EXPRESSION IN IMMUNOGLOBULIN-TRANSGENIC MICE - EVIDENCE FOR SELECTION OF ANTIBODY REPERTOIRES

V(H) gene family expression in single cells of the emergent, available and actual B cell repertoires of C57BL/6 mice was compared to that of two immunoglobulin (Ig)-transgenic B6 lines (B6-Sp6 and M54). We found that < 5% of bone marrow cells of transgenic mice express endogenous V(H) genes and that the vast majority (95%) of the peripheral, mature B cell repertoire in these animals is composed of cells expressing the V(H)J558 transgenic family. Unimmunized transgenic mice, however, diversify V(H) gene family usage by 'background' Ig-secreting cells in the spleen, > 50% of which express endogenous V(H) genes. The pattern of endogenous V(H) gene family expression in the actual repertoire of B6-Sp6 mice is indistinguishable from that of normal B6 mice. In contrast, actual repertoires of M54 mice differ by a 4- to 5-fold higher representation of the V(H)Q52 family. These results demonstrate a powerful positive selection of B cells into the secretory compartments of unimmunized animals, show that actual and available repertoires differ very markedly, and suggest that V region interactions participate in the selection of 'natural antibody' repertoires.