V(H) CDR3-DEPENDENT POSITIVE SELECTION OF MURINE V(H)12-EXPRESSING B-CELLS IN THE NEONATE

被引:33
作者
CLARKE, SH [1 ]
MCCRAY, SK [1 ]
机构
[1] UNIV N CAROLINA,CURRICULUM GENET & MOLEC BIOL,CHAPEL HILL,NC 27514
关键词
V(H)2; ANTI-PHOSPHATIDYLCHOLINE; POSITIVE SELECTION;
D O I
10.1002/eji.1830231240
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Five to fifteen percent of peritoneal B 1 (CD5+) cells from unmanipulated mice produce antibodies that bind bromelain-treated mouse red blood cells and the hapten phosphatidylcholine (PtC). The majority of these B cells express either of two V(H)/Nkappa gene combinations, V(H)12/Vkappa4 or V(H)11/Vkappa9. Both the V(H)11 and V(H)12 genes are rearranged to JH1 and encode third complementarity determining regions (CDR3) of restricted length and sequence. These and other observations argue strongly that PtC-specific B1 cells are antigen selected. To determine when selection of PtC-specific B1 cells begins in mice we have used the polymerase chain reaction to amplify V(H)12-D-J(H)I rearrangements from livers of fetal and neonatal mice, and determined the CDR3 encoding sequences of individual clones. We find an unusually low ratio of productive (P) to non-productive (NP) rearrangements (0.4 - 1.0) at both developmental stages. P rearrangements in day 1 neonates are biased in D gene use and in the sequence and length of their deduced V(H) CDR3. These biases are similar to those of PtC-specific B1 cells in the adult peritoneum. D gene use and CDR3 length and sequence are significantly less biased among V(H)12 P rearrangements 2 to 3 days earlier in the day 18 fetal liver. We suggest that this rapid change in repertoire is due to positive ligand selection that is dependent on the sequence of VH CDR3.We suggest further that the majority Of V(H)12-expressing cells are not ligand selected and consequently undergo programmed cell death. The evidence of restriction in day 1 neonatal livers and the low P/NP ratio in the fetus suggests that selection Of V(H)12-expressing cells begins before birth.
引用
收藏
页码:3327 / 3334
页数:8
相关论文
共 40 条
[1]  
BOOKER JK, 1992, ANN NY ACAD SCI, V651, P498
[2]   DEVELOPMENTALLY CONTROLLED SELECTION OF ANTIBODY GENES - CHARACTERIZATION OF INDIVIDUAL VH7183 GENES AND EVIDENCE FOR STAGE-SPECIFIC SOMATIC DIVERSIFICATION [J].
CARLSSON, L ;
OVERMO, C ;
HOLMBERG, D .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1992, 22 (01) :71-78
[3]  
CARLSSON L, 1990, INT IMMUNOL, V2, P639, DOI 10.1093/intimm/2.7.639
[4]   REARRANGEMENT AND SELECTION OF VH11 IN THE LY-1 B-CELL LINEAGE [J].
CARMACK, CE ;
SHINTON, SA ;
HAYAKAWA, K ;
HARDY, RR .
JOURNAL OF EXPERIMENTAL MEDICINE, 1990, 172 (01) :371-374
[5]   ENUMERATION AND CHARACTERIZATION OF DJH STRUCTURES IN MOUSE FETAL LIVER [J].
CHANG, Y ;
PAIGE, CJ ;
WU, GE .
EMBO JOURNAL, 1992, 11 (05) :1891-1899
[6]   THE OMEGA/DELTA-5-SURROGATE IMMUNOGLOBULIN LIGHT CHAIN IS EXPRESSED ON THE SURFACE OF TRANSITIONAL LYMPHOCYTES-B IN MURINE BONE-MARROW [J].
CHERAYIL, BJ ;
PILLAI, S .
JOURNAL OF EXPERIMENTAL MEDICINE, 1991, 173 (01) :111-116
[7]  
COX KO, 1985, IMMUNOLOGY, V55, P263
[8]  
DECKER DJ, 1991, J IMMUNOL, V147, P1406
[9]  
DECKER DJ, 1991, J IMMUNOL, V146, P350
[10]   EXPRESSION OF ANTI-DNA IMMUNOGLOBULIN TRANSGENES IN NON-AUTOIMMUNE MICE [J].
ERIKSON, J ;
RADIC, MZ ;
CAMPER, SA ;
HARDY, RR ;
CARMACK, C ;
WEIGERT, M .
NATURE, 1991, 349 (6307) :331-334