The pre-B cell receptor and its role in proliferation and Ig heavy chain allelic exclusion

2002 ◽  
Vol 14 (5) ◽  
pp. 335-342 ◽  
Author(s):  
Inga-Lill Mårtensson ◽  
Antonius Rolink ◽  
Fritz Melchers ◽  
Cornelia Mundt ◽  
Steve Licence ◽  
...  
Keyword(s):  
B Cell ◽  
Heavy Chain ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Allelic Exclusion ◽  
Ig Heavy Chain

scholarly journals Characterization of B-cell Receptor Heavy Chain Complementarity-determining Region 3 Repertoire Based on the Differences of Symbiotic Microorganisms in the Gut of Mice

2021 ◽  
Author(s):  
Jun Li ◽  
Yurong Pan ◽  
Qingqing Ma ◽  
Long Ma ◽  
Bin Shi ◽  
...  
Keyword(s):  
Small Intestine ◽  
B Cells ◽  
B Cell ◽  
Heavy Chain ◽  
Intestinal Microflora ◽  
Cell Receptor ◽  
Memory B Cells ◽  
B Cell Receptor ◽  
Positive Effects ◽  
Significant Difference

Abstract Background Colonization of gut microorganism is related to maturation of B cells in peripheral immune organs. This study aims to investigate the effect of intestinal microflora in Germ-free (GF), Specific Pathogen-free (SPF) and Clean (CL) BALB/C mice to small intestine total B-cell and memory B-cell receptor (BCR) complementary-determining region 3 (CDR3) repertoire. Results The composition and characteristics of intestinal microflora were analyzed by 16S rDNA sequencing. Genomic DNA extracted from small intestine tissue and memory B-cells of GF, SPF and CL mice were conducted via high-throughput DNA sequencing methods. As expected, significant differences of gut microflora diversity were observed in the three mice groups. CL group showed the most diversity, followed by SPF group, and GF group had the lowest diversity. Moreover, anormogenesis of intestinal lymphoid tissue were observed in GF mice. Diversity of the BCR heavy chain CDR3 repertoire in memory B cells were significant difference among three groups, but not in total B cells. The nucleotide polymorphism, usage frequency of gene segments (V, D, J, V–J gene segments) and amino acid of total B cells and memory B cells CDR3 were comparable among three mice groups, and there was significant difference between CL and GF mice groups. Conclusions The results of this study advocate that the colonization of intestinal microorganisms affect the diversity of B cells CDR3 repertoire. Elucidating mechanism of microbiome participated in the function of intestinal mucosal immune system may have positive effects on human health, and it requires further investigation.

scholarly journals Immunoglobulin and T cell receptor gene configuration in acute lymphoblastic leukemia of infancy

Blood ◽  
1987 ◽  
Vol 70 (2) ◽  
pp. 536-541 ◽  
Author(s):  
CA Felix ◽  
GH Reaman ◽  
SJ Korsmeyer ◽  
GF Hollis ◽  
PA Dinndorf ◽  
...  
Keyword(s):  
B Cell ◽  
T Cell Receptor ◽  
Heavy Chain ◽  
Light Chain ◽  
Lymphoblastic Leukemia ◽  
Cell Receptor ◽  
Chain Gene ◽  
Heavy Chain Gene ◽  
Cell Precursor ◽  
Ig Heavy Chain

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.

scholarly journals Expression Levels of B Cell Surface Immunoglobulin Regulate Efficiency of Allelic Exclusion and Size of Autoreactive B-1 Cell Compartment

1999 ◽  
Vol 190 (4) ◽  
pp. 461-470 ◽  
Author(s):  
Norihiko Watanabe ◽  
Sazuku Nisitani ◽  
Koichi Ikuta ◽  
Misao Suzuki ◽  
Tsutomu Chiba ◽  
...  
Keyword(s):  
B Cell ◽  
Critical Role ◽  
Cell Subset ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Receptor Expression ◽  
Chain Gene ◽  
Allelic Exclusion ◽  
Cell Compartment ◽  
Self Antigens

Surface-expressed immunoglobulin (Ig) has been shown to have a critical role in allelic exclusion of Ig heavy (H) and light (L) chains. Although various degrees of suppression of endogenous Ig expression are observed in Ig transgenic (Tg) mice, it was not clear whether this difference is due to different onsets of Tg expression or to different levels of Tg expression, which are obviously affected by integration sites of the transgene. In this study we generated antierythrocyte antibody Tg mice that carry tandem joined H and L chain transgenes (H+L) and confirmed that homozygosity of the transgene loci enhances the level of transgene expression as compared with heterozygosity. Suppression of endogenous H and L chain gene expression was stronger in homozygous than in heterozygous Tg mice. Similar results were obtained in control Tg mice carrying the H chain only. These results suggest that there is a threshold of the B cell receptor expression level that induces allelic exclusion. In addition, despite the same B cell receptor specificity, the size of Tg autoreactive B-1 cell compartment in the peritoneal cavity is larger in homozygous than in heterozygous mice, although the number of the Tg B-2 cell subset decreased in the spleen and bone marrow of homozygous Tg mice as compared with heterozygous Tg mice. By contrast, homozygosity of the H chain alone Tg line, which does not recognize self-antigens, did not increase the size of the peritoneal B-1 subset. These results suggest that the size of the B-1 cell subset in the Tg mice may depend on strength of signals through B cell receptors triggered by self-antigens.

scholarly journals Immunoglobulin heavy chains are sufficient to determine most B cell clonal relationships1

2019 ◽  
Author(s):  
Julian Q. Zhou ◽  
Steven H. Kleinstein
Keyword(s):  
B Cell ◽  
High Throughput ◽  
Heavy Chain ◽  
Clonal Expansion ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Light Chains ◽  
Heavy Chains ◽  
Computational Inference ◽  
Cell Clonal Expansion

AbstractB cell clonal expansion is vital for adaptive immunity. High-throughput B cell receptor (BCR) sequencing enables investigating this process, but requires computational inference to identify clonal relationships. This inference usually relies on only the BCR heavy chain, as most current protocols do not preserve heavy:light chain pairing. The extent to which paired light chains aids inference is unknown. Using human single-cell paired BCR datasets, we assessed the ability of heavy chain-based clonal clustering to identify clones. Of the expanded clones identified, <20% grouped cells expressing inconsistent light chains. Heavy chains from these misclustered clones contained more distant junction sequences and shared fewer V segment mutations than the accurate clones. This suggests that additional heavy chain information could be leveraged to refine clonal relationships. Conversely, light chains were insufficient to refine heavy chain-based clonal clusters. Overall, the BCR heavy chain alone is sufficient to identify clonal relationships with confidence.

scholarly journals Variable heavy-chain gene analysis of follicular lymphomas: subclone selection rather than clonal evolution over time

Blood ◽  
2001 ◽  
Vol 98 (1) ◽  
pp. 238-240 ◽  
Author(s):  
Wilhelmina M. Aarts ◽  
Richard J. Bende ◽  
Janneke G. Bossenbroek ◽  
Steven T. Pals ◽  
Carel J. M. van Noesel
Keyword(s):  
B Cell ◽  
Heavy Chain ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Chain Gene ◽  
Variable Heavy ◽  
Vh Gene ◽  
Follicular Lymphomas ◽  
Receptor Evolution ◽  
Over Time

Abstract To investigate B-cell receptor evolution in follicular lymphomas (FLs), immunoglobulin variable heavy chain (VH) gene regions of 3 FLs were analyzed at different time points. One FL with a high somatic mutation load and intraclonal VH gene diversity was investigated in situ. VH gene transcripts were amplified and sequenced from samples of approximately 50 tumor cells isolated from frozen tissue sections by laser microdissection. Interestingly, the mutation pattern of the prevalent subclone in the relapse biopsy was virtually identical to that of a subclone isolated by microdissection from the presentation biopsy 9 years earlier. In a second FL, proof was obtained that the subclone that dominated the relapse sample had already been present in the initial biopsy. The finding that subclones found in the relapses of these FLs had not evolved over time but were preexistent, challenges the concept of antigen-driven B-cell receptor evolution during disease course.

scholarly journals Loss of Precursor B Cell Expansion but Not Allelic Exclusion in VpreB1/VpreB2 Double-Deficient Mice

2001 ◽  
Vol 193 (4) ◽  
pp. 435-446 ◽  
Author(s):  
Cornelia Mundt ◽  
Steve Licence ◽  
Takeyuki Shimizu ◽  
Fritz Melchers ◽  
Inga-Lill Mårtensson
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Receptor ◽  
Allelic Exclusion ◽  
Surrogate Light Chain ◽  
Heavy Chains ◽  
Immature B Cells ◽  
Ig Heavy Chain ◽  
Deficient Mice

The pre-B cell receptor consists of immunoglobulin (Ig) μ heavy chains and surrogate light chain, i.e., the VpreB and λ5 proteins. To analyze the role of the two VpreB proteins, mice lacking the VpreB1 and VpreB2 genes were generated. VpreB1−/−VpreB2−/− mice were impaired in their B cell development at the transition from pre-BI to large pre-BII cells. Pre-BII cells did not expand by proliferation, consequently 40-fold less small pre-BII and immature B cells were found in bone marrow, and the generation of immature and mature conventional B cells in spleen appeared reduced. In addition, only low numbers of B-1a cells were detected in the peritoneum. Surprisingly, Ig heavy chain allelic exclusion was still active, apparently ruling out a signaling role of a VpreB1/VpreB2–containing receptor in this process.

scholarly journals Lack of Allelic Exclusion in B Cell Chronic Lymphocytic Leukemia

1997 ◽  
Vol 185 (8) ◽  
pp. 1435-1446 ◽  
Author(s):  
Laura Z. Rassenti ◽  
Thomas J. Kipps
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Heavy Chain ◽  
Protein A ◽  
Lymphocytic Leukemia ◽  
Allelic Exclusion ◽  
Staphylococcal Protein A ◽  
Vh Genes ◽  
Ig Heavy Chain ◽  
Cell Chronic Lymphocytic Leukemia

We determined the immunoglobulin (Ig) VH subgroup expressed by the leukemia cells of 108 patients with B cell chronic lymphocytic leukemia (CLL). Surprisingly, we found that six samples (5%) each expressed Ig of more than one VH subgroup. Southern blot analysis demonstrated that these samples each had rearrangements involving both Ig heavy chain alleles. Nucleic acid sequence analyses of the Ig cDNA revealed each to express two functional Ig VH genes: VH3-33 and VH4-39; VH3-7 and VH4-39; VH3-23 and VH4-61; VH2-70 and VH3-30.3; or VH3-30 and VH4-b (DP67). One sample expressed three Ig VH genes: VH2-70, VH3-7, and VH4-59. Despite having more than one Ig heavy chain transcript, each sample was found to express only one functional Ig light chain. From the primary sequence, we deduced that the Ig of some of these CLL samples should react with Lc1, a monoclonal antibody (mAb) reactive with a supratypic cross-reactive idiotype present on Ig encoded by a subgroup of Ig VH4 genes (namely, VH4-39, VH4-b [DP-67], VH4-59, or VH4-61), and B6, an mAb that reacts with Ig encoded by certain Ig VH3 genes (namely, VH3-23, VH3-30, or VH3-30.3), and/or modified staphylococcal protein A (SpA), a 45-kilodalton bacterial “superantigen” that reacts with most Ig of the VH3 subgroup. Flow cytometric analyses revealed that such samples did in fact react with Lc1 and B6 and/or SpA, but not with control mAbs of irrelevant specificity. This study demonstrates that a subset of CLL patients have leukemic B cells that express more than one functional Ig heavy chain.

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