scholarly journals A deletion map of the human immunoglobulin heavy chain variable region.

1991 ◽  
Vol 174 (2) ◽  
pp. 335-349 ◽  
Author(s):  
M A Walter ◽  
H M Dosch ◽  
D W Cox
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Heavy Chain ◽  
Normal Population ◽  
Gene Segment ◽  
Variable Region ◽  
Immunoglobulin Heavy Chain ◽  
Racial Groups ◽  
Vh Gene ◽  
Segment Order

Analysis of VH gene segments deleted in the process of immunoglobulin heavy chain (IGH) variable region assembly in three series of monoclonal B cell lines has been used to determine the human VH region organization. A deletion map of the relative positions of 21 different VH gene segments has been determined. The characterization of B cell lines from three unrelated adults of two racial groups yielded the same relative VH gene segment order, suggesting that the overall order of VH genes in the normal population is constant. This VH gene segment order was consistent with what we had previously generated from physical mapping techniques. DH segments from the second DH cluster, distinct from the major DH locus 3' of the VH region, were not observed to be used in 32 different rearrangements. Approximately 77% of the VH-(D)JH rearrangements involved VH gene segments within 500 kb of the JH region, indicating that human B cell lines preferentially rearrange JH-proximal VH gene segments. The switch, observed in mice, from the fetal use of JH-proximal VH gene segments to an adult VH use dependent upon VH family size may therefore not occur in humans. This detailed map of the VH gene segments is a necessary prerequisite for understanding VH usage in development and disease.

scholarly journals Rate of replication of the murine immunoglobulin heavy-chain locus: evidence that the region is part of a single replicon.

1987 ◽  
Vol 7 (1) ◽  
pp. 450-457 ◽  
Author(s):  
E H Brown ◽  
M A Iqbal ◽  
S Stuart ◽  
K S Hatton ◽  
J Valinsky ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Line ◽  
Gene Cluster ◽  
Cell Lines ◽  
Heavy Chain ◽  
Dna Content ◽  
Immunoglobulin Heavy Chain ◽  
S Phase ◽  
C Value ◽  
Murine Erythroleukemia

We measured the temporal order of replication of EcoRI segments from the murine immunoglobulin heavy-chain constant region (IgCH) gene cluster, including the joining (J) and diversity (D) loci and encompassing approximately 300 kilobases. The relative concentrations of EcoRI segments in bromouracil-labeled DNA that replicated during selected intervals of the S phase in Friend virus-transformed murine erythroleukemia (MEL) cells were measured. From these results, we calculated the nuclear DNA content (C value; the haploid DNA content of a cell in the G1 phase of the cell cycle) at the time each segment replicated during the S phase. We observed that IgCH genes replicate in the following order: alpha, epsilon, gamma 2a, gamma 2b, gamma 1, gamma 3, delta, and mu, followed by the J and D segments. The C value at which each segment replicates increased as a linear function of its distance from C alpha. The average rate of DNA replication in the IgCH gene cluster was determined from these data to be 1.7 to 1.9 kilobases/min, similar to the rate measured for mammalian replicons by autoradiography and electron microscopy (for a review, see H. J. Edenberg and J. A. Huberman, Annu. Rev. Genet. 9:245-284, 1975, and R. G. Martin, Adv. Cancer Res. 34:1-55, 1981). Similar results were obtained with other murine non-B cell lines, including a fibroblast cell line (L60T) and a hepatoma cell line (Hepa 1.6). In contrast, we observed that IgCh segments in a B-cell plasmacytoma (MPC11) and two Abelson murine leukemia virus-transformed pre-B cell lines (22D6 and 300-19O) replicated as early as (300-19P) or earlier than (MPC11 and 22D6) C alpha in MEL cells. Unlike MEL cells, however, all of the IgCH segments in a given B cell line replicated at very similar times during the S phase, so that a temporal directionality in the replication of the IgCH gene cluster was not apparent from these data. These results provide evidence that in murine non-B cells the IgCH, J, and D loci are part of a single replicon.

Immunoglobulin heavy-chain enhancer is required to maintain transfected gamma 2A gene expression in a pre-B-cell line

1990 ◽  
Vol 10 (3) ◽  
pp. 1076-1083
Author(s):  
B Porton ◽  
D M Zaller ◽  
R Lieberson ◽  
L A Eckhardt
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Heavy Chain ◽  
Gene Activation ◽  
Immunoglobulin Heavy Chain ◽  
Transcription Unit ◽  
Enhancer Activity ◽  
Igh Genes ◽  
High Level

The immunoglobulin heavy-chain (IgH) enhancer serves to activate efficient and accurate transcription of cloned IgH genes when introduced into B lymphomas or myelomas. The role of this enhancer after gene activation, however, is unclear. The endogenous IgH genes in several cell lines, for example, have lost the IgH enhancer by deletion and yet continue to be expressed. This might be explained if the role of the enhancer were to establish high-level gene transcription but not to maintain it. Alternatively, other enhancers might lie adjacent to endogenous IgH genes, substituting their activity for that of the lost IgH enhancer. To address both of these alternatives, we searched for enhancer activity within the flanking regions of one of these IgH enhancer-independent genes and designed an experiment that allowed us to consider separately the establishment and maintenance of expression of a transfected gene. For the latter experiment we generated numerous pre-B cell lines stably transformed with a gamma 2a gene. In this gene, the IgH enhancer lay at a site outside the heavy-chain transcription unit, between DH and JH gene segments. After expression of the transfected gene was established, selective conditions were chosen for the outgrowth of subclones that had undergone D-J joining and thus IgH enhancer deletion. Measurements of gamma 2a expression before and after enhancer deletion revealed that the enhancer was required for maintenance of expression of the transfected gene. The implication of this finding for models of enhancer function in endogenous genes is discussed.

Immunoglobulin heavy chain variable region family expression in primary cutaneous B-cell lymphomas

2001 ◽  
Vol 145 (4) ◽  
pp. 680-680 ◽  
Author(s):  
F.J. Child ◽  
R. Russell-Jones ◽  
A.J. Woolford ◽  
E. Calonje ◽  
S.J. Whittaker
Keyword(s):  
B Cell ◽  
Heavy Chain ◽  
Variable Region ◽  
Immunoglobulin Heavy Chain ◽  
B Cell Lymphomas ◽  
Heavy Chain Variable Region

scholarly journals Overusage of Mouse DH Gene Segment, DFL16.1, Is Strain-Dependent and Determined bycis-Acting Elements

1994 ◽  
Vol 3 (4) ◽  
pp. 283-295 ◽  
Author(s):  
Michael J. Atkinson ◽  
Yenhui Chang ◽  
Jakub W. Celler ◽  
Carol Huang ◽  
Christopher J. Paige ◽  
...  
Keyword(s):  
B Cells ◽  
Genetic Analysis ◽  
Cell Lines ◽  
Heavy Chain ◽  
High Frequency ◽  
Fetal Liver ◽  
Gene Segment ◽  
Immunoglobulin Heavy Chain ◽  
Strain Dependent ◽  
Is Strain

The DJH structure is of particular importance for diversity in the immunoglobulin heavy chain because it encodes most of CDR3. Here, we investigate mechanisms responsible for generating the DJH structure. We found DFL16.1 was used at a high frequency in normal and transformed pre-B cells (fetal liver > 50%, A-MuLV lines ≅ 25%). One DFL16.1JH1 structure was found repeatedly and was also present in DJH and VDJH databases, suggesting this structure may be conserved in the primary repertoire. Genetic analysis demonstrated that C57BL/6 mice use DFL16.1 in DJH structures more frequently than BALB/c. Examination of individual alleles in (C57BL/6 BALB/c)F1 A-MuLV cell lines revealed that the C57BL/6-derived allele used DFL16.1 twice as often as the BALB/c. This result indicates that part of the mechanism ensuring overusage of DFL16.1 gene segments iscis-acting.

scholarly journals The immunoglobulin heavy chain locus contains another B-cell-specific 3' enhancer close to the alpha constant region.

1993 ◽  
Vol 13 (3) ◽  
pp. 1547-1553 ◽  
Author(s):  
P Matthias ◽  
D Baltimore
Keyword(s):  
Transcription Factors ◽  
B Cell ◽  
Heavy Chain ◽  
Variable Region ◽  
Immunoglobulin Heavy Chain ◽  
Immunoglobulin Genes ◽  
Constant Region ◽  
Transcriptional Enhancer ◽  
Additional Control ◽  
Complex Regulation

The transcription of immunoglobulin genes is controlled by variable region promoters and by enhancers, both of which are lymphoid specific. Because immunoglobulin genes are subject to an extremely complex regulation, we anticipated that there might be additional control elements for these genes. We therefore sought additional enhancers and demonstrate here that there is indeed another weak transcriptional enhancer just 3' to the mouse alpha constant region. This novel immunoglobulin enhancer is lymphoid specific and at two positions can bind members of the Oct family of transcription factors.

Diversity of immunoglobulin heavy chain gene segment rearrangement in B lymphoblastoid cell lines from X-linked agammaglobulinemia patients

1991 ◽  
Vol 21 (10) ◽  
pp. 2355-2363 ◽  
Author(s):  
Erik Timmers ◽  
Marcel Kenter ◽  
Allan Thompson ◽  
Margriet E. M. Kraakman ◽  
Jeffrey E. Berman ◽  
...  
Keyword(s):  
Cell Lines ◽  
Heavy Chain ◽  
Gene Segment ◽  
Immunoglobulin Heavy Chain ◽  
Chain Gene ◽  
Lymphoblastoid Cell Lines ◽  
Heavy Chain Gene ◽  
Immunoglobulin Heavy Chain Gene
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