Restricted utilization of germ-line VH3 genes and short diverse third complementarity-determining regions (CDR3) in human fetal B lymphocyte immunoglobulin heavy chain rearrangements

1992 ◽  
Vol 22 (1) ◽  
pp. 247-251 ◽  
Author(s):  
Frank M. Raaphorst ◽  
Erik Timmers ◽  
Marcel J. H. Kenter ◽  
Maarten J. D. Van Tol ◽  
Jaak M. Vossen ◽  
...  
Keyword(s):  
Heavy Chain ◽  
B Lymphocyte ◽  
Germ Line ◽  
Immunoglobulin Heavy Chain ◽  
Complementarity Determining Regions

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 Pan/E2A expression precedes immunoglobulin heavy-chain expression during B lymphopoiesis in nontransformed cells, and Pan/E2A proteins are not detected in myeloid cells.

1994 ◽  
Vol 14 (6) ◽  
pp. 4087-4096 ◽  
Author(s):  
Y Jacobs ◽  
X Q Xin ◽  
K Dorshkind ◽  
C Nelson
Keyword(s):  
B Cell ◽  
Cell Line ◽  
Heavy Chain ◽  
B Lymphocyte ◽  
Myeloid Cells ◽  
Immunoglobulin Heavy Chain ◽  
Cell Development ◽  
B Cell Development ◽  
Chain Gene ◽  
Enhancer Element

A newly developed rat long-term bone marrow culture system was used to study the role of Pan/E2A basic helix-loop-helix transcription factors during B-cell development. In this system, B-lymphocyte progenitors actively differentiate into mature B cells. Monoclonal (Yae) and polyclonal (anti-Pan) antibodies were employed to characterize the expression of Pan proteins by Western blot assay during hematopoiesis and to examine the components of immunoglobulin heavy-chain gene enhancer element-binding species by electrophoretic mobility shift assay. During B-cell development, the appearance of Pan/E2A proteins preceded the expression of immunoglobulin heavy-chain protein. A Pan-containing immunoglobulin heavy-chain enhancer element (mu E5)-binding species (BCF1), composed of immunoreactive Pan-1/E47 but not Pan-2/E12, was observed concomitantly with the detection of Pan/E2A proteins. In addition to BCF1, other mu E5-binding species were detected which were not recognized by the Yae antibody. Two of these species were present in primary B-lymphocyte and myeloid cultures and were recognized by an anti-upstream stimulatory factor antiserum. Although Pan/E2A proteins have been proposed to be ubiquitous, Pan/E2A proteins were not detected in primary myeloid cultures composed mainly of granulocytes and macrophages or in the macrophage cell line J774. The absence of Pan/E2A proteins in differentiated myeloid cells correlated with low steady-state levels of Pan/E2A RNA. However, Pan/E2A proteins were present in a promyeloid cell line, 32DCL3, suggesting that extinction of Pan/E2A expression may play a role in myelopoiesis.

scholarly journals Germ-line genetic variation in the immunoglobulin heavy chain creates stroke susceptibility in the spontaneously hypertensive rat

2019 ◽  
Vol 51 (11) ◽  
pp. 578-585 ◽  
Author(s):  
Isha S. Dhande ◽  
Sterling C. Kneedler ◽  
Aniket S. Joshi ◽  
Yaming Zhu ◽  
M. John Hicks ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Cerebrovascular Disease ◽  
Heavy Chain ◽  
Antibody Formation ◽  
Stress Proteins ◽  
Germ Line ◽  
Spontaneously Hypertensive Rat ◽  
Immunoglobulin Heavy Chain ◽  
Congenic Line ◽  
Spontaneously Hypertensive

The risk of cerebrovascular disease in stroke-prone spontaneously hypertensive rats (SHR-A3/SHRSP) arises from naturally occurring genetic variation. In the present study we show the involvement of SHR genetic variation that affects antibody formation and function in the pathogenesis of stroke. We have tested the involvement in susceptibility to stroke of genetic variation in IgH, the gene encoding the immunoglobulin heavy chain by congenic substitution. This gene contains functional natural variation in SHR-A3 that diverges from stroke-resistant SHR-B2. We created a SHR-A3 congenic line in which the IgH gene was substituted with the corresponding haplotype from SHR-B2. Compared with SHR-A3 rats, congenic substitution of the IgH locus [SHR-A3( IgH-B2)] markedly reduced cerebrovascular disease. Given the role in antibody formation of the IgH gene, we investigated the presence of IgG and IgM autoantibodies and their targets using a high-density protein array containing ~20,000 recombinant proteins. High titers of autoantibodies to key cerebrovascular stress proteins were detected, including FABP4, HSP70, and Wnt signaling proteins. Serum levels of these autoantibodies were reduced in the SHR-A3( IgH-B2) congenic line.

Structure and expression of germ line immunoglobulin heavy-chain epsilon transcripts: interleukin-4 plus lipopolysaccharide-directed switching to C epsilon

1990 ◽  
Vol 10 (4) ◽  
pp. 1672-1679
Author(s):  
P Rothman ◽  
Y Y Chen ◽  
S Lutzker ◽  
S C Li ◽  
V Stewart ◽  
...  
Keyword(s):  
Heavy Chain ◽  
Germ Line ◽  
General Structure ◽  
Immunoglobulin Heavy Chain ◽  
Transcription Unit ◽  
Lymphoid Cells ◽  
Interleukin 4 ◽  
Cdna Clones ◽  
Similar Treatment ◽  
B Lymphoid

We have isolated cDNA clones complementary to a truncated immunoglobulin heavy-chain C epsilon RNA transcript previously found to be induced in B lymphoid cells by treatment with lipopolysaccharide (LPS) combined with interleukin-4 (IL-4). We demonstrate that this transcript initiates from a promoter upstream of the germ line epsilon class-switch recombination region (S epsilon region). The major germ line C epsilon transcript contains a small 5' exon contributed by sequences upstream of the S epsilon region spliced to the normal C epsilon exons. Treatment of splenic B lymphoid cells with LPS plus IL-4 induces the expression of transcripts from the germ line epsilon transcription unit followed by expression of normal immunoglobulin epsilon heavy-chain mRNA. Furthermore, we demonstrate that similar treatment of transformed precursor B cell lines induces the expression of germ line epsilon transcripts followed by class switching to epsilon expression in these lines. This is the first demonstration of switching to epsilon in cells of the pre-B stage. The general structure of the germ line epsilon transcript and transcription unit is similar to that previously characterized for germ line gamma 2b transcripts. However, expression of these two germ line transcription units in B-lineage cells is inversely regulated by IL-4 (plus LPS) treatment, correlating with the effects of these treatments on switching to these loci.

scholarly journals The V(D)J recombinational and transcriptional activities of the immunoglobulin heavy-chain intronic enhancer can be mediated through distinct protein-binding sites in a transgenic substrate.

1995 ◽  
Vol 15 (6) ◽  
pp. 3217-3226 ◽  
Author(s):  
C Fernex ◽  
M Capone ◽  
P Ferrier
Keyword(s):  
Heavy Chain ◽  
Transcriptional Activation ◽  
Germ Line ◽  
Receptor Gene ◽  
Immunoglobulin Heavy Chain ◽  
Cell Receptor ◽  
Regulatory Sequences ◽  
Intronic Enhancer ◽  
Molecular Events ◽  
Activation Of Transcription

Immunoglobulin and T-cell receptor gene transcriptional enhancers encompass sequences which stimulate V(D)J recombination of associated variable gene segments. To address the question of whether enhancer-mediated transcriptional activation and recombinational activation depend on the same cis-regulatory sequences, we have produced transgenic mice by using recombination substrates containing various mutations in the immunoglobulin heavy-chain intronic enhancer (E mu). Analysis of substrate rearrangements indicated that specific compound elements including E-box transcriptional motifs are crucial for the recombinational activity of E mu in the developing B and T lymphocytes. In most cases, a faithful correlation between the levels of substrate germ line transcription and recombination was observed. However, some of the E mu mutants which were able to activate transcription of the unrearranged substrate were inefficient in stimulating transgene recombination, implying that the latter function depends on molecular events other than the mere activation of transcription and that both activities can be mediated through distinct regulatory sequences. Together, these results support a model in which lymphoid gene enhancers, in addition to providing docking sites for factors that dictate transcriptional accessibility, must have some specific function(s) for activating V(D)J recombination.

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