scholarly journals Responding kinetic of B-cell receptor repertoire to the Toll-like receptor 7/8 stimulation in non-human primates

2021 ◽  
Author(s):  
Shiyu Wang ◽  
Judith Mandl ◽  
Mark Feinberg ◽  
Michael Citron ◽  
Nitin K. Saksena ◽  
...  
Keyword(s):  
B Cell ◽  
Mutation Rate ◽  
Cell Activation ◽  
Rhesus Macaques ◽  
Low Frequency ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Receptor Repertoire ◽  
Cell Immunity ◽  
Repertoire Diversity

TLR7 and 8 regulate B cell immunity, but the precise details of the mechanism are still unclear. Here, we studied the kinetics of both heavy and light chains (IgKL) of B-cell receptor (BCR) repertoire responding to the TLR7/8 stimulation in two geniuses of non-human primates (NHPs), African green monkeys (AGMs) and rhesus macaques (RMs). We evaluated the activation of lymphocytes by flow cytometry and studied characteristics of BCR repertoire in terms of gene usage, repertoire diversity, and the number of lineages. Although AGMs had a weaker activation than RMs, and a different responding kinetic, both AGMs and RMs presented an increased IgKL repertoire diversity and lineages expansion. It suggested that the responding time rather than initiation of TLR7/8-induced IgKL repertoire response related to B cell activation. Expanded IgKL lineages with frequency from 0.001% to 1% had an elevated mutation rate and expanded IgH lineages used more IgA/G/E, suggesting that the TLR7/8 stimulation expanded low-frequent but high-mutated lineages. Besides, most of expanded IgKL lineages were lambda isotype. In conclusion, TLR7/8 selectively expands IgKL lineages with a high mutation rate, low frequency, and lambda isotype. The selective effect of TLR7/8 on BCR repertoire allows TLR7/8 agonists to be adjuvant for selectively accelerating antibody maturation.

scholarly journals Antigens Varying in Affinity for the B Cell Receptor Induce Differential B Lymphocyte Responses

1998 ◽  
Vol 188 (8) ◽  
pp. 1453-1464 ◽  
Author(s):  
Valerie Kouskoff ◽  
Sara Famiglietti ◽  
Georges Lacaud ◽  
Paul Lang ◽  
James E. Rider ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
B Cell ◽  
Cell Activation ◽  
B Lymphocyte ◽  
Receptor Occupancy ◽  
Cell Receptor ◽  
Interferon Γ ◽  
B Cell Receptor ◽  
Multiple Parameters ◽  
Biological Responses

The B cell receptor (BCR) triggers a variety of biological responses that differ depending upon the properties of the antigen. A panel of M13 phage-displayed peptide ligands with varying affinity for the 3-83 antibody was generated to explore the role of antigen-BCR affinity in cell activation studies using primary 3-83 transgenic mouse B cells. Multiple parameters of activation were measured. T cell–independent B cell proliferation, antibody secretion, induction of germline immunoglobulin γ1 transcripts, and B cell production of interleukin (IL) 2 and interferon γ responses were better correlated with antigen-BCR affinity than with receptor occupancy. In contrast, other responses, such as upregulation of major histocompatibility complex class II and B7.2 (CD86), secretion of IL-6, and B cell proliferation in the context of CD40 signaling were only weakly dependent on antigen affinity. Biochemical analysis revealed that at saturating ligand concentrations the ability of phage to stimulate some early signaling responses, such as Ca++ mobilization and tyrosine phosphorylation of syk or Igα, was highly affinity dependent, whereas the ability to stimulate Lyn phosphorylation was less so. These data suggest that the BCR is capable of differential signaling. The possibility that differential BCR signaling by antigen determines whether an antibody response will be T independent or dependent is discussed.

scholarly journals Signatures of B Cell Receptor Repertoire Following Pneumocystis Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Han Sun ◽  
Hu-Qin Yang ◽  
Kan Zhai ◽  
Zhao-Hui Tong
Keyword(s):  
B Cells ◽  
B Cell ◽  
Single Cell ◽  
Plasma Cells ◽  
Somatic Hypermutation ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Receptor Repertoire ◽  
Elevated Expression ◽  
Pneumocystis Infection

B cells play vital roles in host defense against Pneumocystis infection. However, the features of the B cell receptor (BCR) repertoire in disease progression remain unclear. Here, we integrated single-cell RNA sequencing and single-cell BCR sequencing of immune cells from mouse lungs in an uninfected state and 1–4 weeks post-infection in order to illustrate the dynamic nature of B cell responses during Pneumocystis infection. We identified continuously increased plasma cells and an elevated ratio of (IgA + IgG) to (IgD + IgM) after infection. Moreover, Pneumocystis infection was associated with an increasing naïve B subset characterized by elevated expression of the transcription factor ATF3. The proportion of clonal expanded cells progressively increased, while BCR diversity decreased. Plasma cells exhibited higher levels of somatic hypermutation than naïve B cells. Biased usage of V(D)J genes was observed, and the usage frequency of IGHV9-3 rose. Overall, these results present a detailed atlas of B cell transcriptional changes and BCR repertoire features in the context of Pneumocystis infection, which provides valuable information for finding diagnostic biomarkers and developing potential immunotherapeutic targets.

scholarly journals Functional Outcome of B Cell Activation by Chromatin Immune Complex Engagement of the B Cell Receptor and TLR9

2007 ◽  
Vol 179 (11) ◽  
pp. 7397-7405 ◽  
Author(s):  
Liliana Busconi ◽  
Jason W. Bauer ◽  
Joseph R. Tumang ◽  
Amy Laws ◽  
Kristin Perkins-Mesires ◽  
...  
Keyword(s):  
B Cell ◽  
Functional Outcome ◽  
Immune Complex ◽  
Cell Activation ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
B Cell Activation

scholarly journals PTIP chromatin regulator controls development and activation of B cell subsets to license humoral immunity in mice

2017 ◽  
Vol 114 (44) ◽  
pp. E9328-E9337 ◽  
Author(s):  
Dan Su ◽  
Stijn Vanhee ◽  
Rebeca Soria ◽  
Elin Jaensson Gyllenbäck ◽  
Linda M. Starnes ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Humoral Immunity ◽  
Cell Activation ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Transactivation Domain ◽  
B Cell Activation ◽  
Chromatin Regulator ◽  
B Cell Subsets

B cell receptor signaling and downstream NF-κB activity are crucial for the maturation and functionality of all major B cell subsets, yet the molecular players in these signaling events are not fully understood. Here we use several genetically modified mouse models to demonstrate that expression of the multifunctional BRCT (BRCA1 C-terminal) domain-containing PTIP (Pax transactivation domain-interacting protein) chromatin regulator is controlled by B cell activation and potentiates steady-state and postimmune antibody production in vivo. By examining the effects of PTIP deficiency in mice at various ages during ontogeny, we demonstrate that PTIP promotes bone marrow B cell development as well as the neonatal establishment and subsequent long-term maintenance of self-reactive B-1 B cells. Furthermore, we find that PTIP is required for B cell receptor- and T:B interaction-induced proliferation, differentiation of follicular B cells during germinal center formation, and normal signaling through the classical NF-κB pathway. Together with the previously identified role for PTIP in promoting sterile transcription at the Igh locus, the present results establish PTIP as a licensing factor for humoral immunity that acts at several junctures of B lineage maturation and effector cell differentiation by controlling B cell activation.

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