VH11 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 receptor genes, leading to an absence of T and B lymphocytes in most SCID mice. However, the SCID phenotype is "leaky", with an age- and strain-dependent increase in the incidence of mice with small number of T and B cells and readily detectable serum immunoglobulin. Introduction of neonatal T cells into young SCID mice results in a 100% incidence of the leaky phenotype. We have identified the location of antibody secreting cells in T cell-induced leaky SCID mice as the spleen and peritoneal cavity, and we have sequenced 35 productively rearranged immunoglobulin genes from these sites to determine if normal V-D-J recombination was occurring. VH11 sequences with potential autoreactivity were observed frequently in both the peritoneal cavity and spleen of T cell-induced leaky SCID mice, and these sequences were indistinguishable from those recovered from peritoneal cavity B cells from normal C.B-17 mice. Non-VH11 SCID sequences showed fewer N nucleotides and slightly more P nucleotides than normal V-D-J sequences. Many SCID junctions occurred at the site of short sequence homologies. These results suggest that successful V-D-J recombination is occurring with low frequency in all SCID mice, and that neonatal T cell transfer plus autoantigen stimulation allows the long term survival of these B cells.
Riggs
J E
JE
Department of Biology, Rider College, Lawrenceville, NJ 08648.
Feeney
A J
AJ
Kirven
M
M
Mosier
D E
DE
D000818:Animals; D000921:Antibody-Producing Cells; D001483:Base Sequence; D004797:Enzyme-Linked Immunosorbent Assay; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000637:transplantation
D007135:Immunoglobulin Variable Region