scholarly journals Isotype-specific Selection of High Affinity Memory B Cells in Nasal-associated Lymphoid Tissue

2001 ◽  
Vol 194 (11) ◽  
pp. 1597-1608 ◽  
Author(s):  
Michiko Shimoda ◽  
Toru Nakamura ◽  
Yoshimasa Takahashi ◽  
Hideki Asanuma ◽  
Shin-ichi Tamura ◽  
...  
Keyword(s):  
B Cells ◽  
Heavy Chain ◽  
Lymphoid Tissue ◽  
Cell Activation ◽  
Affinity Maturation ◽  
Memory B Cells ◽  
Constant Region ◽  
B Cell Activation ◽  
High Affinity ◽  
Heavy Chain Constant Region

Mucosal immunoglobulin (Ig)A dominance has been proposed to be associated with preferential class switch recombination (CSR) to the IgA heavy chain constant region, Cα. Here, we report that B cell activation in nasal-associated lymphoid tissue (NALT) upon stimulation with the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP) coupled to chicken γ globulin caused an anti-NP memory response dominated by high affinity IgA antibodies. In the response, however, NP-specific IgG+ B cells expanded and sustained their number as a major population in germinal centers (GCs), supporting the view that CSR to IgG heavy chain constant region, Cγ, operated efficiently in NALT. Both IgG+ and IgA+ GC B cells accumulated somatic mutations, indicative of affinity maturation to a similar extent, suggesting that both types of cell were equally selected by antigen. Despite the selection in GCs, high affinity NP-specific B cells were barely detected in the IgG memory compartment, whereas such cells dominated the IgA memory compartment. Taken together with the analysis of the VH gene clonotype in GC and memory B cells, we propose that NALT is equipped with a unique machinery providing IgA-specific enrichment of high affinity cells into the memory compartment, facilitating immunity with high affinity and noninflammatory secretory antibodies.

scholarly journals Requirement for memory B-cell activation in protection from heterologous influenza virus reinfection

2019 ◽  
Vol 31 (12) ◽  
pp. 771-779 ◽  
Author(s):  
Sarah Leach ◽  
Ryo Shinnakasu ◽  
Yu Adachi ◽  
Masatoshi Momota ◽  
Chieko Makino-Okamura ◽  
...  
Keyword(s):  
Influenza Virus ◽  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Influenza Infection ◽  
Memory B Cells ◽  
B Cell Activation ◽  
Memory B Cell

Memory B cells protect against heterologous influenza infection

scholarly journals SWAP-70 deficiency causes high-affinity plasma cell generation despite impaired germinal center formation

Blood ◽  
2008 ◽  
Vol 111 (5) ◽  
pp. 2714-2724 ◽  
Author(s):  
Laurence Quemeneur ◽  
Veronique Angeli ◽  
Michael Chopin ◽  
Rolf Jessberger
Keyword(s):  
B Cells ◽  
Plasma Cell ◽  
Cell Activation ◽  
Plasma Cells ◽  
Actin Binding ◽  
B Cell Activation ◽  
Interacting Protein ◽  
Memory Response ◽  
High Affinity

Germinal centers (GCs) are lymphoid tissue structures central to the generation of long-lived, high-affinity, antibody-forming B cells. However, induction, maintenance, and regulation of GCs are not sufficiently understood. The F-actin–binding, Rac-interacting protein SWAP-70 is strongly expressed in activated B cells like those in B follicles. Recent work suggests that SWAP-70 is involved in B-cell activation, migration, and homing. Therefore, we investigated the role of SWAP-70 in the T-dependent immune response, in GC formation, and in differentiation into plasma and memory B cells. Compared with wt, sheep red blood cell (SRBC)–, or NP-KLH–immunized SWAP-70−/− mice have strongly reduced numbers of GCs and GC-specific B cells. However, SWAP-70−/− NP-specific B cells accumulate outside of the B follicles, and SWAP-70−/− mice show more plasma cells in the red pulp and in the bone marrow, and increased NP-specific Ig and antibody-forming B cells. Yet the memory response is impaired. Thus, SWAP-70 deficiency uncouples GC formation from T-dependent antibody and long-lived plasma cell production and causes extrafollicular generation of high-affinity plasma cells, but does not adequately support the memory response.

scholarly journals Selective dysregulation of the FcγIIB receptor on memory B cells in SLE

2006 ◽  
Vol 203 (9) ◽  
pp. 2157-2164 ◽  
Author(s):  
Meggan Mackay ◽  
Anfisa Stanevsky ◽  
Tao Wang ◽  
Cynthia Aranow ◽  
Margaret Li ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Cell Receptor ◽  
Memory B Cells ◽  
Therapeutic Interventions ◽  
B Cell Activation ◽  
Loss Of Self ◽  
Novel Target

The inappropriate expansion and activation of autoreactive memory B cells and plasmablasts contributes to loss of self-tolerance in systemic lupus erythematosus (SLE). Defects in the inhibitory Fc receptor, FcγRIIB, have been shown to contribute to B cell activation and autoimmunity in several mouse models of SLE. In this paper, we demonstrate that expression of FcγRIIB is routinely up-regulated on memory B cells in the peripheral blood of healthy controls, whereas up-regulation of FcγRIIB is considerably decreased in memory B cells of SLE patients. This directly correlates with decreased FcγRIIB-mediated suppression of B cell receptor–induced calcium (Ca2+) response in those B cells. We also found substantial overrepresentation of African-American patients among those who failed to up-regulate FcγRIIB. These results suggest that the inhibitory receptor, FcγRIIB, may be impaired at a critical checkpoint in SLE in the regulation of memory B cells; thus, FcγRIIB represents a novel target for therapeutic interventions in this disease.

scholarly journals Human B Cell Activation by Autologous NK Cells Is Regulated by CD40-CD40 Ligand Interaction: Role of Memory B Cells and CD5+B Cells

2001 ◽  
Vol 167 (11) ◽  
pp. 6132-6139 ◽  
Author(s):  
Isaac R. Blanca ◽  
Earl W. Bere ◽  
Howard A. Young ◽  
John R. Ortaldo
Keyword(s):  
B Cells ◽  
B Cell ◽  
Nk Cells ◽  
Cell Activation ◽  
Cd40 Ligand ◽  
Memory B Cells ◽  
B Cell Activation ◽  
Ligand Interaction ◽  
Human B Cell

scholarly journals Positive Selection in the Light Zone of Germinal Centers

2021 ◽  
Vol 12 ◽  
Author(s):  
Rinako Nakagawa ◽  
Dinis Pedro Calado
Keyword(s):  
B Cells ◽  
Positive Selection ◽  
B Cell ◽  
Plasma Cells ◽  
Selection Process ◽  
Germinal Centers ◽  
Affinity Maturation ◽  
Memory B Cells ◽  
Cell Fates ◽  
High Affinity

Germinal centers (GCs) are essential sites for the production of high-affinity antibody secreting plasma cells (PCs) and memory-B cells (MBCs), which form the framework of vaccination. Affinity maturation and permissive selection in GCs are key for the production of PCs and MBCs, respectively. For these purposes, GCs positively select “fit” cells in the light zone of the GC and instructs them for one of three known B cell fates: PCs, MBCs and persistent GC-B cells as dark zone entrants. In this review, we provide an overview of the positive selection process and discuss its mechanisms and how B cell fates are instructed.

scholarly journals CD4+T Cells Promote Antibody Production but Not Sustained Affinity Maturation during Borrelia burgdorferi Infection

2014 ◽  
Vol 83 (1) ◽  
pp. 48-56 ◽  
Author(s):  
Rebecca A. Elsner ◽  
Christine J. Hastey ◽  
Nicole Baumgarth
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Cd4 T Cells ◽  
Plasma Cells ◽  
Affinity Maturation ◽  
Memory B Cells ◽  
Antibody Responses ◽  
Content Type ◽  
High Affinity

CD4 T cells are crucial for enhancing B cell-mediated immunity, supporting the induction of high-affinity, class-switched antibody responses, long-lived plasma cells, and memory B cells. Previous studies showed that the immune response toBorrelia burgdorferiappears to lack robust T-dependent B cell responses, as neither long-lived plasma cells nor memory B cells form for months after infection, and nonswitched IgM antibodies are produced continuously during this chronic disease. These data prompted us to evaluate the induction and functionality ofB. burgdorferiinfection-induced CD4 TFHcells. We report that CD4 T cells were effectively primed and TFHcells induced afterB. burgdorferiinfection. These CD4 T cells contributed to the control ofB. burgdorferiburden and supported the induction ofB. burgdorferi-specific IgG responses. However, while affinity maturation of antibodies against a prototypic T-dependentB. burgdorferiprotein, Arthritis-related protein (Arp), were initiated, these increases were reversed later, coinciding with the previously observed involution of germinal centers. The cessation of affinity maturation was not due to the appearance of inhibitory or exhausted CD4 T cells or a strong induction of regulatory T cells.In vitroT-B cocultures demonstrated that T cells isolated fromB. burgdorferi-infected but notB. burgdorferi-immunized mice supported the rapid differentiation of B cells into antibody-secreting plasma cells rather than continued proliferation, mirroring the induction of rapid short-lived instead of long-lived T-dependent antibody responsesin vivo. The data further suggest thatB. burgdorferiinfection drives the humoral response away from protective, high-affinity, and long-lived antibody responses and toward the rapid induction of strongly induced, short-lived antibodies of limited efficacy.

Abatacept Reduces Levels of Switched Memory B Cells, Autoantibodies, and Immunoglobulins in Patients with Rheumatoid Arthritis

2014 ◽  
Vol 41 (4) ◽  
pp. 666-672 ◽  
Author(s):  
Mirko Scarsi ◽  
Lucia Paolini ◽  
Doris Ricotta ◽  
Antonio Pedrini ◽  
Silvia Piantoni ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Activation ◽  
Serum Levels ◽  
Memory B Cells ◽  
Cell Phenotype ◽  
B Cell Activation ◽  
Switch Memory

Objective.Abatacept (ABA) is a chimeric molecule, able to block the CD28-mediated costimulatory pathway. To evaluate the hypothesis that, through this mechanism of action, ABA may down-modulate the immune responses of B lymphocytes in rheumatoid arthritis (RA), we investigated the serum levels of immunoglobulins (Ig), free light chains (FLC), anticitrullinated protein antibodies (ACPA), and rheumatoid factor (RF), as well as the number of B lymphocytes differentiated into post-switch memory cells in patients treated with ABA.Methods.The serum levels of Ig, FLC, different ACPA, RF isotypes, and the B cell phenotype were longitudinally evaluated in 30 patients with RA treated with ABA.Results.At baseline, the proportion of total and post-switch memory B cells was lower in RA than in healthy individuals. After 6 months of ABA treatment we observed significant reductions of serum levels of IgG, IgA, and IgM, as well as FLC, with a normalization in many patients who had initially abnormal values. A significant reduction of the titers of IgG- and IgA-ACPA, as well as of IgM-, IgA-, and IgG-RF was also observed. A decrease of autoantibodies below the upper limits of normal values was found in 2 of 26 patients (8%) initially seropositive for IgG-ACPA, 1 of 14 (7%) for IgA-ACPA, 5 of 22 (23%) for IgM-RF, 7 of 22 (30%) for IgA-RF, and 5 of 16 (31%) for IgG-RF. After treatment, the proportion of circulating post-switch memory B cells was also further significantly decreased.Conclusion.ABA treatment in patients with RA can reduce signs of polyclonal B cell activation, inducing a trend toward normalization of serum levels of different classes of Ig and of FLC, decreasing titers of ACPA and RF, and percentages of post-switch memory B cells.

scholarly journals IL-21 in Conjunction with Anti-CD40 and IL-4 Constitutes a Potent Polyclonal B Cell Stimulator for Monitoring Antigen-Specific Memory B Cells

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 433
Author(s):  
Fridolin Franke ◽  
Greg A. Kirchenbaum ◽  
Stefanie Kuerten ◽  
Paul V. Lehmann
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Immune Monitoring ◽  
Memory B Cells ◽  
B Cell Activation ◽  
Cell Stimulation ◽  
Additional Advantage ◽  
Specific Memory

Detection of antigen-specific memory B cells for immune monitoring requires their activation, and is commonly accomplished through stimulation with the TLR7/8 agonist R848 and IL-2. To this end, we evaluated whether addition of IL-21 would further enhance this TLR-driven stimulation approach; which it did not. More importantly, as most antigen-specific B cell responses are T cell-driven, we sought to devise a polyclonal B cell stimulation protocol that closely mimics T cell help. Herein, we report that the combination of agonistic anti-CD40, IL-4 and IL-21 affords polyclonal B cell stimulation that was comparable to R848 and IL-2 for detection of influenza-specific memory B cells. An additional advantage of anti-CD40, IL-4 and IL-21 stimulation is the selective activation of IgM+ memory B cells, as well as the elicitation of IgE+ ASC, which the former fails to do. Thereby, we introduce a protocol that mimics physiological B cell activation through helper T cells, including induction of all Ig classes, for immune monitoring of antigen-specific B cell memory.

scholarly journals Somatic Hypermutation Shapes the Antibody Repertoire of Memory B Cells in Humans

2001 ◽  
Vol 194 (3) ◽  
pp. 375-378 ◽  
Author(s):  
Eric Meffre ◽  
Nadia Catalan ◽  
Françoise Seltz ◽  
Alain Fischer ◽  
Michel C. Nussenzweig ◽  
...  
Keyword(s):  
B Cells ◽  
Significant Contribution ◽  
Somatic Hypermutation ◽  
Cytidine Deaminase ◽  
Affinity Maturation ◽  
Memory B Cells ◽  
Antibody Repertoire ◽  
Lambda Light Chain ◽  
High Affinity ◽  
Activation Induced Cytidine Deaminase

High-affinity antibodies produced by memory B cells differ from antibodies produced in naive B cells in two respects. First, many of these antibodies show somatic hypermutation, and second, the repertoire of antibodies expressed in memory responses is highly selected. To determine whether somatic hypermutation is responsible for the shift in the antibody repertoire during affinity maturation, we analyzed the immunoglobulin lambda light chain (Igλ) repertoire expressed by naive and antigen-selected memory B cells in humans. We found that the Igλ repertoire differs between naive and memory B cells and that this shift in the repertoire does not occur in the absence of somatic hypermutation in patients lacking activation-induced cytidine deaminase (AID). Our work suggests that somatic hypermutation makes a significant contribution to shaping the antigen-selected antibody repertoire in humans.

scholarly journals Polyclonal B cell activation for accurate analysis of pre-existing antigen-specific memory B cells

2014 ◽  
Vol 177 (1) ◽  
pp. 333-340 ◽  
Author(s):  
G. E. Karahan ◽  
M. Eikmans ◽  
J. D. H. Anholts ◽  
F. H. J. Claas ◽  
S. Heidt
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Memory B Cells ◽  
B Cell Activation ◽  
Accurate Analysis ◽  
Specific Memory
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