V(H)11 BIAS AND NORMAL V-D-J JUNCTIONS IN SCID B-LYMPHOCYTES RESCUED BY NEONATAL T-CELL TRANSFER

The scid mutation interferes with normal rearrangement of antigen rece ptor genes, leading to an absence of T and B lymphocytes in most SCID mice. However, the SCID phenotype is ''leaky'', with an age- and strai n-dependent increase in the incidence of mice with small numbers of T and B cells and readily detectable serum immunoglobulin. Introduction of neonatal T cells into young SCID mice results in a 100% incidence o f the leaky phenotype. We have identified the location of antibody sec reting cells in T cell-induced leaky SCID mice as the spleen and perit oneal cavity, and we have sequenced 35 productively rearranged immunog lobulin genes from these sites to determine if normal V-D-J recombinat ion was occurring. V(H)11 sequences with potential autoreactivity were observed frequently in both the peritoneal cavity and spleen of T cel l-induced leaky SCID mice, and these sequences were indistinguishable from those recovered from peritoneal cavity B cells from normal C.B-17 mice. Non-V(H)11 SCID sequences showed fewer N nucleotides and slight ly more P nucleotides than normal V-D-J sequences. Many SCID junctions occurred at the site of short sequence homologies. These results sugg est that successful V-D-J recombination is occurring with low frequenc y in all SCID mice, and that neonatal T cell transfer plus autoantigen stimulation allows the long term survival of these B cells.