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.

The diversity of rearranged immunoglobulin heavy chain variable region genes in peripheral blood B cells of preterm infants is restricted by short third complementarity-determining regions but not by limited gene segment usage

Blood ◽  
2001 ◽  
Vol 97 (5) ◽  
pp. 1511-1513 ◽  
Author(s):  
Michael Zemlin ◽  
Karl Bauer ◽  
Michael Hummel ◽  
Sabine Pfeiffer ◽  
Simone Devers ◽  
...  
Keyword(s):  
B Cells ◽  
Preterm Infants ◽  
Heavy Chain ◽  
Peripheral Blood ◽  
Gene Segment ◽  
Immunoglobulin Heavy Chain ◽  
Term Infants ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
Complementarity Determining Regions

The immunoglobulin diversity is restricted in fetal liver B cells. This study examined whether peripheral blood B cells of extremely preterm infants show similar restrictions (overrepresentation of some gene segments, short third complementarity-determining regions [CDR3]). DNA of rearranged immunoglobulin heavy chain genes was amplified by polymerase chain reaction, cloned, and sequenced. A total of 417 sequences were analyzed from 6 preterm infants (25-28 weeks of gestation), 6 term infants, and 6 adults. Gene segments from the entire VHand DH gene locus were rearranged in preterm infants, even though the DH7-27 segment was overrepresented (17% of rearrangements) compared to term infants (7%) and adults (2%). CDR3 was shorter in preterm infants (40 ± 10 nucleotides) than in term infants (44 ± 12) and adults (48 ± 14) (P < .001) due to shorter N regions. Somatic mutations were exclusively found in term neonates and adults (mutational frequency 0.8% and 1.8%). We conclude that preterm infants have no limitations in gene segment usage, whereas the diversity of CDR3 is restricted throughout gestation.

scholarly journals B cell progenitors have different growth requirements before and after immunoglobulin heavy chain commitment.

1988 ◽  
Vol 168 (4) ◽  
pp. 1511-1516 ◽  
Author(s):  
H Sauter ◽  
C J Paige
Keyword(s):  
B Cells ◽  
B Cell ◽  
Heavy Chain ◽  
Fetal Liver ◽  
Immunoglobulin Heavy Chain ◽  
Growth Conditions ◽  
Selective Growth ◽  
Cell Assay ◽  
Growth Requirements ◽  
Before And After

Using the clonable pre-B cell assay, we have identified B cell progenitors that are not yet committed to the production of a particular H chain allele. These cells represent approximately 10-20% of clonable pre-B cells found in 15-d fetal liver. The clonable pre-B cell assay provides an environment adequate for the expansion and differentiation of these cells into mature, Ig-secreting, cells. Using the same methodology, we have also identified progenitors that are uncommitted to the production of a particular L chain isotype. Moreover, investigating the growth requirements for clonable pre-B cells has led to the discovery of selective growth conditions that distinguish cells before and after commitment to H chain allotype.

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

scholarly journals VH1–46 Is the Dominant Immunoglobulin Heavy Chain Gene Segment in Rotavirus-Specific Memory B Cells Expressing the Intestinal Homing Receptor α4β7

2005 ◽  
Vol 174 (6) ◽  
pp. 3454-3460 ◽  
Author(s):  
Jörn-Hendrik Weitkamp ◽  
Nicole L. Kallewaard ◽  
Amber L. Bowen ◽  
Bonnie J. LaFleur ◽  
Harry B. Greenberg ◽  
...  
Keyword(s):  
B Cells ◽  
Heavy Chain ◽  
Gene Segment ◽  
Immunoglobulin Heavy Chain ◽  
Memory B Cells ◽  
Chain Gene ◽  
Heavy Chain Gene ◽  
Immunoglobulin Heavy Chain Gene ◽  
Homing Receptor ◽  
Specific Memory

scholarly journals Murine hematopoietic cells with pre-B or pre-B/myeloid characteristics are generated by in vitro transformation with retroviruses containing fes, ras, abl, and src oncogenes.

1986 ◽  
Vol 164 (2) ◽  
pp. 443-457 ◽  
Author(s):  
K L Holmes ◽  
J H Pierce ◽  
W F Davidson ◽  
H C Morse
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
Cell Lines ◽  
Heavy Chain ◽  
Fetal Liver ◽  
Chain Locus ◽  
Fetal Liver Cells ◽  
B Lineage ◽  
Ig Heavy Chain

In vitro infection of bone marrow or fetal liver cells with retroviruses containing fes, abl, ras, or src oncogenes resulted in the transformation of early B lineage cells. All cell lines tested possessed rearrangements at the Ig heavy chain locus and some had rearrangements at the K chain locus. The majority of the lines corresponded phenotypically to Lyb-2+, Ly-5(B220)+, ThB- large pre-B cells, although some were classified as pro-B cells because of their Lyb-2+, Ly-17+, Ly-5(B220)- phenotype. We identified two cell lines that contained subpopulations of cells that coexpressed the B lineage antigens Lyb-2 and Ly-5(B220) and the myeloid lineage antigen Mac-1. Single-cell FMF cloning of these subpopulations showed that Mac-1+ cells were derived from Mac-1- cells and that these Mac-1+-cloned cells further differentiated into cells with phenotypic and functional characteristics of mature macrophages.

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 Inversions produced during V(D)J rearrangement at IgH, the immunoglobulin heavy-chain locus.

1995 ◽  
Vol 15 (2) ◽  
pp. 671-681 ◽  
Author(s):  
A E Sollbach ◽  
G E Wu
Keyword(s):  
Heavy Chain ◽  
Adult Mouse ◽  
Fetal Liver ◽  
Immunoglobulin Heavy Chain ◽  
Antigen Receptors ◽  
Adult Mice ◽  
Chain Locus ◽  
Heavy Chain Locus ◽  
Fetal Liver Cells

Diversity in immunoglobulin antigen receptors is generated in part by V(D)J recombination. In this process, different combinations of gene elements are joined in various configurations. Products of V(D)J recombination are coding joints, signal joints, and hybrid junctions, which are generated by deletion or inversion. To determine their role in the generation of diversity, we have examined two sorts of recombination products, coding joints and hybrid junctions, that have formed by inversion at the mouse immunoglobulin heavy-chain locus. We developed a PCR assay for quantification and characterization of inverted rearrangements of DH and JH gene elements. In primary cells from adult mice, inverted DJH rearrangements are detectable but they are rare. There were approximately 1,100 to 2,200 inverted DJH coding joints and inverted DJH hybrid junctions in the marrow of one adult mouse femur. On day 16 of gestation, inverted DJH rearrangements are more abundant. There are approximately 20,000 inverted DJH coding joints and inverted DJH hybrid junctions per day 16 fetal liver. In fetal liver cells, the number of inverted DJH rearrangements remains relatively constant from day 14 to day 16 of gestation. Inverted DJH rearrangements to JH4, the most 3' JH element, are more frequently detected than inverted DJH rearrangements to other JH elements. We compare the frequencies of inverted DJH rearrangements to previously determined frequencies of uninverted DJH rearrangements (DJH rearrangements formed by deletion). We suggest that inverted DJH rearrangements are influenced by V(D)J recombination mechanistic constraints and cellular selection.

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.

scholarly journals Immunoglobulin gene rearrangements in normal mouse B cells

1982 ◽  
Vol 2 (7) ◽  
pp. 829-836
Author(s):  
P Early ◽  
C Nottenburg ◽  
I Weissman ◽  
L Hood
Keyword(s):  
B Cells ◽  
Heavy Chain ◽  
Germ Line ◽  
Gene Segment ◽  
Immunoglobulin M ◽  
Chain Gene ◽  
Allelic Exclusion ◽  
Immunoglobulin Gene ◽  
Spleen Cells ◽  
Surface Immunoglobulin

We have analyzed the structure of rearranged mu heavy-chain genes obtained from the genomic DNA of normal BALB/c mouse spleen cells expressing surface immunoglobulin M. Examples were found of two types of nonproductive rearrangements, which may be responsible for allelic exclusion in normal B cells. In one of these rearrangements, a germ line D gene segment has joined to the JH4 gene segment but no V/D joining has occurred. We present evidence that D gene segments lie as a cluster between V and J gene segments in the germ line. A comparison of conserved sequences in V and D gene segments suggests that the D gene segments, which are found only in the heavy-chain gene family, may have evolved from V gene segments similar to the Vk family.

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