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

被引:3
作者
RIGGS, JE
FEENEY, AJ
KIRVEN, M
MOSIER, DE
机构
[1] Scripps Res Inst, DEPT IMMUNOL IMM22, LA JOLLA, CA 92037 USA
[2] RIDER COLL, DEPT BIOL, LAWRENCEVILLE, NJ 08648 USA
[3] Scripps Res Inst, DEPT IMMUNOL IMM7, LA JOLLA, CA 92037 USA
关键词
SCID; V-D-J RECOMBINATION; VH BIAS;
D O I
10.1016/0161-5890(94)90016-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 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 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. V(H)11 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-V(H)11 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.
引用
收藏
页码:783 / 791
页数:9
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