scholarly journals The Initiation of B Cell Clonal Expansion Occurs Independently of Pre-B Cell Receptor Formation

2001 ◽  
Vol 167 (9) ◽  
pp. 5136-5142 ◽  
Author(s):  
Gregory H. Kline ◽  
Tracy A. Hayden ◽  
Patricia Riegert
Keyword(s):  
B Cell ◽  
Clonal Expansion ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Cell Clonal Expansion

scholarly journals A p53 Axis Regulates B Cell Receptor-Triggered, Innate Immune System-Driven B Cell Clonal Expansion

2012 ◽  
Vol 188 (12) ◽  
pp. 6093-6108 ◽  
Author(s):  
Hyunjoo Lee ◽  
Shabirul Haque ◽  
Jennifer Nieto ◽  
Joshua Trott ◽  
John K. Inman ◽  
...  
Keyword(s):  
Immune System ◽  
B Cell ◽  
Innate Immune System ◽  
Clonal Expansion ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Innate Immune ◽  
Cell Clonal Expansion

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 Anti–HIV-1 B cell responses are dependent on B cell precursor frequency and antigen-binding affinity

2018 ◽  
Vol 115 (18) ◽  
pp. 4743-4748 ◽  
Author(s):  
Pia Dosenovic ◽  
Ervin E. Kara ◽  
Anna-Klara Pettersson ◽  
Andrew T. McGuire ◽  
Matthew Gray ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Neutralizing Antibodies ◽  
Single Cells ◽  
Clonal Expansion ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Precursor Frequency ◽  
Anti Hiv ◽  
Hiv 1

The discovery that humans can produce potent broadly neutralizing antibodies (bNAbs) to several different epitopes on the HIV-1 spike has reinvigorated efforts to develop an antibody-based HIV-1 vaccine. Antibody cloning from single cells revealed that nearly all bNAbs show unusual features that could help explain why it has not been possible to elicit them by traditional vaccination and instead would require a sequence of different immunogens. This idea is supported by experiments with genetically modified immunoglobulin (Ig) knock-in mice. Sequential immunization with a series of specifically designed immunogens was required to shepherd the development of bNAbs. However, knock-in mice contain superphysiologic numbers of bNAb precursor-expressing B cells, and therefore how these results can be translated to a more physiologic setting remains to be determined. Here we make use of adoptive transfer experiments using knock-in B cells that carry a synthetic intermediate in the pathway to anti–HIV-1 bNAb development to examine how the relationship between B cell receptor affinity and precursor frequency affects germinal center (GC) B cell recruitment and clonal expansion. Immunization with soluble HIV-1 antigens can recruit bNAb precursor B cells to the GC when there are as few as 10 such cells per mouse. However, at low precursor frequencies, the extent of clonal expansion is directly proportional to the affinity of the antigen for the B cell receptor, and recruitment to GCs is variable and dependent on recirculation.

scholarly journals The B-Cell Receptor of Primary Cutaneous Follicle Center Lymphoma: Implications for Pathogenesis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4136-4136
Author(s):  
Marvyn T. Koning ◽  
Sander A.J. van der Zeeuw ◽  
Willem H. Zoutman ◽  
Maarten H. Vermeer ◽  
Rein Willemze ◽  
...  
Keyword(s):  
B Cell ◽  
De Novo ◽  
Class Switch Recombination ◽  
B Cell Lymphoma ◽  
Clonal Expansion ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Full Length ◽  
Sequence Motifs ◽  
Class Switch

Abstract Introduction & Objectives: Primary Cutaneous Follicle Center Lymphoma (PCFCL) is a very indolent mature B-cell lymphoma that shares germinal center (GC) morphology with follicular lymphoma (FL) but lacks the characteristic t(14;18). Unlike FL, immunohistochemistry fails to detect expression of BCL2, CD10, and immunoglobulin in PCFCL. We investigated the B-cell receptor (BCR) to gain insight into the immunobiology of PCFCL. Materials & Methods: Whole Genome Sequencing (WGS) and RNAseq were performed on five PCFCL biopsies. Full-length heavy and light chain BCR transcripts were amplified by unbiased ARTISAN PCR (Koning et al., BJH 2016). More than 2000 sequences per BCR transcript were sequenced as full-length single molecules on the PacBio next-generation sequencing platform. Results: In addition to various minor translocations and deletions, WGSidentified a t(14;22) that resulted in juxtaposition of IGH and IGLL5 in one PCFCL case. No PCFCL case carried a t(14;18). Despite the absence of detectable surface Ig by immunohistochemistry, ARTISAN PCR and RNAseq-based de novo BCR assembly independently demonstrated expression of functional VDJ and VJ genes with heavily mutated V regions (VDJ: 7,1-16,0%; VJ: 4,6-11,1%) in all cases. Lack of intraclonal sequence variation indicated absence of ongoing somatic hypermutation (SHM). The t(14;22)-carrying PCFCL expressed an inconspicuous IgM. BCR of all remaining four PCFCL carried sequence motifs for N-linked glycosylation in antigen-binding regions that were apparently acquired by SHM. Three cases had undergone class switch recombination to IgG. The remaining case expressed IgM with extensive mutations. An L265P mutation in MYD88 was identified in one case, and two cases carried amplifications in chromosome 2 involving the proto-oncogene REL. Conclusions: GC morphology, extensive SHM, and class switch recombination indicate a shared origin of GC B cells for both PCFCL and FL. Clonal BCR sequences and previously identified copy number alterations prove that PCFCL represents a neoplastic clonal expansion. However, lack of ongoing SHM indicates that the immune follicles of PCFCL are not fully functional germinal centers. Since ongoing SHM is thought to contribute to lymphomagenesis by targeting non-BCR loci, absence of both ongoing SHM and the t(14;18) may explain the relatively benign clinical course of PCFCL compared to FL. As previously described for FL, continuous BCR stimulation through glycosylation-mediated binding of lectins on resident cells of the follicular microenvironment may cause clonal expansion of PCFCL cells and could play a decisive role in maintaining the follicular microarchitecture in both FL and PCFCL. In comparison to this BCR glycosylation, acquired somatic alterations in oncogenes that recurrently involved in other types of indolent B-cell lymphomas may constitute secondary driver events. Further comparisons to define the extent of malignant transformation between PCFCL, FL, and other B-lymphomas are warranted. Disclosures Vermeer: Innate Pharma: Other: Investigator in a clinical trial.

B cell receptor editing in tolerance and autoimmunity

10.2741/2217 ◽  
2007 ◽  
Vol 12 (1) ◽  
pp. 2136 ◽  
Author(s):  
Hilla Azulay-Debby
Keyword(s):  
B Cell ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Receptor Editing
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