scholarly journals Evidence That Terminal Deoxynucleotidyltransferase Expression Plays a Role in Ig Heavy Chain Gene Segment Utilization

2000 ◽  
Vol 164 (12) ◽  
pp. 6387-6397 ◽  
Author(s):  
Nadine Tuaillon ◽  
J. Donald Capra
2001 ◽  
Vol 22 (7) ◽  
pp. 400-405 ◽  
Author(s):  
Kimberly D. Klonowski ◽  
Marc Monestier

Blood ◽  
1987 ◽  
Vol 70 (2) ◽  
pp. 536-541 ◽  
Author(s):  
CA Felix ◽  
GH Reaman ◽  
SJ Korsmeyer ◽  
GF Hollis ◽  
PA Dinndorf ◽  
...  

Abstract We examined immunoglobulin (Ig) heavy chain, K light chain, and T cell receptor (TCR) gamma and beta gene configuration in the leukemic cells from a series of infants aged less than 1 year with acute lymphoblastic leukemia (ALL). Each of these 11 cases demonstrated leukemic cell surface antigens that have been correlated with a B cell precursor phenotype. Of the 11, lymphoblasts of 4 retained the germline configuration of both Ig and TCR loci, whereas 7 had rearranged the Ig heavy chain gene. Two of these seven showed light chain gene rearrangement. TCB beta chain rearrangement had occurred in only one of the 11 patients' tumors. No TCR gamma chain rearrangements were identified. These results are in contrast to earlier studies of B cell precursor ALL in children in which Ig heavy chain gene rearrangements were evident in every case and approximately 40% showed Ig light chain rearrangement as well. In addition, 45% of cases of B cell precursor ALL of children had rearranged their gamma TCR genes, and 20% had rearranged beta. These data suggest that ALL in infancy represents an earlier stage of B cell development than is found in B cell precursor ALL of children. ALL in the infant age group has been associated with the worst prognosis of all patients with ALL. This study suggests that the disease in infants differs not only clinically, but also at the molecular genetic level, from the disease in children.


1988 ◽  
Vol 167 (6) ◽  
pp. 1969-1974 ◽  
Author(s):  
M C Nussenzweig ◽  
A C Shaw ◽  
E Sinn ◽  
J Campos-Torres ◽  
P Leder

Expression of the membrane-bound version of the human mu chain in transgenic mice results in the allelic exclusion of endogenous mouse Ig heavy chain genes (6). The secreted version of the human Ig transgene has no such effect. F1 hybrid animals that carry transgenes for both secreted and membrane-bound human mu chains produce both forms of the human heavy chain while strongly suppressing endogenous mouse mu expression. The simultaneous expression of the two rearranged transgenes in primary B cells suggests that allelic exclusion operates before the formation of a second functionally rearranged heavy chain gene in vivo.


1993 ◽  
Vol 13 (11) ◽  
pp. 7163-7169
Author(s):  
R R Rivera ◽  
M H Stuiver ◽  
R Steenbergen ◽  
C Murre

We used a DNA-protein interaction screening method to isolate a cDNA, Erg-3, whose product binds to a site, designated pi, present in the immunoglobulin (Ig) heavy-chain gene enhancer. Erg-3 is an alternatively spliced product of the erg gene and contains an Ets DNA-binding domain. Fli-1 and PU.1, related Ets proteins, also bind to the same site. In addition, PU.1 binds to a second site, designated microB, in the Ig heavy-chain enhancer. We demonstrate that the pi binding site is crucial for Ig heavy-chain gene enhancer function. In addition, we show that Erg-3 and Fli.1, but not PU.1, can activate a reporter construct containing a multimer of protein-binding sites, synergistically with helix-loop-helix protein E12. We discuss how combinatorial interactions between members of the helix-loop-helix and Ets families may account for the tissue specificity of these proteins.


1991 ◽  
Vol 21 (10) ◽  
pp. 2355-2363 ◽  
Author(s):  
Erik Timmers ◽  
Marcel Kenter ◽  
Allan Thompson ◽  
Margriet E. M. Kraakman ◽  
Jeffrey E. Berman ◽  
...  

Blood ◽  
1993 ◽  
Vol 81 (3) ◽  
pp. 775-782 ◽  
Author(s):  
GR Kitchingman

Abstract Acute lymphoblastic leukemia (ALL) represents the clonal outgrowth of transformed hematopoietic progenitor cells. We have found that blast cells in some cases of B-precursor cell ALL contain Ig heavy chain gene rearrangements with considerable diversity at the junctions of the variable (VH), diversity (D), and joining (JH) regions. This diversity consists of heterogeneous nucleotide sequences at the VH-D and, less frequently, the D-JH junctions. In two cases, different VH segments were attached to the same D-JH rearrangement. In all cases studied there was a much higher than expected frequency of nucleotide sequence changes in the VH segment. At least three mechanisms may produce these changes in different cases: (1) continuing rearrangement of the heavy chain gene, in some cases by VH addition to a preexisting D-JH; (2) VH replacement; and (3) an open-and-shut mechanism. These findings suggest that an active VDJ recombinase system is present at the time of transformation in a high percentage of ALLs. An active recombinase in the rapidly growing leukemic cell population could lead to genomic instability.


1993 ◽  
Vol 13 (11) ◽  
pp. 7163-7169 ◽  
Author(s):  
R R Rivera ◽  
M H Stuiver ◽  
R Steenbergen ◽  
C Murre

We used a DNA-protein interaction screening method to isolate a cDNA, Erg-3, whose product binds to a site, designated pi, present in the immunoglobulin (Ig) heavy-chain gene enhancer. Erg-3 is an alternatively spliced product of the erg gene and contains an Ets DNA-binding domain. Fli-1 and PU.1, related Ets proteins, also bind to the same site. In addition, PU.1 binds to a second site, designated microB, in the Ig heavy-chain enhancer. We demonstrate that the pi binding site is crucial for Ig heavy-chain gene enhancer function. In addition, we show that Erg-3 and Fli.1, but not PU.1, can activate a reporter construct containing a multimer of protein-binding sites, synergistically with helix-loop-helix protein E12. We discuss how combinatorial interactions between members of the helix-loop-helix and Ets families may account for the tissue specificity of these proteins.


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