scholarly journals Recall of B cell memory depends on relative locations of prime and boost

2021 ◽  
Author(s):  
Masayuki Kuraoka ◽  
Chen-Hao Yeh ◽  
Goran Bajic ◽  
Ryutaro Kotaki ◽  
Shengli Song ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Germinal Centers ◽  
Cross Reactivity ◽  
Memory B Cells ◽  
Antigen Receptors ◽  
Vaccination Strategies ◽  
B Cell Memory ◽  
Homologous Antigen ◽  
Heterologous Antigens

Re-entry of memory B cells to recall germinal centers (GCs) is essential for updating their B-cell antigen receptors (BCRs). Using single B-cell culture and fate-mapping, we have characterized BCR repertoires in recall GCs following boost immunizations at sites local or distal to the priming. Local boosts with homologous antigen recruit to recall GCs progeny of primary GC B cells more efficiently than do distal boosts. Recall GCs following local boosts contain significantly more B cells with elevated levels of Ig mutations and higher avidity BCRs. This local preference is unaffected by blockade of CD40:CD154 interaction that terminate active, primary GC responses. Local boosts with heterologous antigens elicit secondary GCs with B-cell populations enriched for cross-reactivity to the priming and boosting antigens; in contrast, cross-reactive GC B cells are rare following distal boosts. Our findings indicate the importance of locality in humoral immunity and inform serial vaccination strategies for evolving viruses.

scholarly journals Human Memory B Cells TargetingStaphylococcus aureusExotoxins Are Prevalent with Skin and Soft Tissue Infection

mBio ◽  
2018 ◽  
Vol 9 (2) ◽  
Author(s):  
Adam J. Pelzek ◽  
Bo Shopsin ◽  
Emily E. Radke ◽  
Kayan Tam ◽  
Beatrix M. Ueberheide ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Acute Phase ◽  
Serum Antibody ◽  
Cross Reactivity ◽  
Memory B Cells ◽  
Host Defenses ◽  
Cell Memory ◽  
B Cell Memory

ABSTRACTStaphylococcus aureusis a Gram-positive opportunistic pathogen that causes superficial and invasive infections in the hospital and community. High mortality from infection emphasizes the need for improved methods for prevention and treatment. AlthoughS. aureuspossesses an arsenal of virulence factors that contribute to evasion of host defenses, few studies have examined long-term humoral and B-cell responses. Adults with acute-phase skin and soft tissue infections were recruited; blood samples were obtained; andS. aureusisolates, including methicillin-resistant strains, were subjected to genomic sequence analysis. In comparisons of acute-phase sera with convalescent-phase sera, a minority (37.5%) of patients displayed 2-fold or greater increases in antibody titers against three or moreS. aureusantigens, whereas nearly half exhibited no changes, despite the presence of toxin genes in most infecting strains. Moreover, enhanced antibody responses waned over time, which could reflect a defect in B-cell memory or long-lived plasma cells. However, memory B cells reactive with a range ofS. aureusantigens were prevalent at both acute-phase and convalescent-phase time points. While some memory B cells exhibited toxin-specific binding, those cross-reactive with structurally related leucocidin subunits were dominant across patients, suggesting the targeting of conserved epitopes. Memory B-cell reactivity correlated with serum antibody levels for selectedS. aureusexotoxins, suggesting a relationship between the cellular and humoral compartments. Overall, although there was no global defect in the representation of anti-S. aureusmemory B cells, there was evidence of restrictions in the range of epitopes recognized, which may suggest potential therapeutic approaches for augmenting host defenses.IMPORTANCEThe contribution of B-cell memory and long-term antibody responses to host defenses againstS. aureusexotoxins remains poorly understood. Our studies confirmed that infection did not commonly lead to enhanced long-term humoral responses. Whereas circulating memory B cells againstS. aureussecreted exotoxins were prevalent, they were dominated by cross-reactivity with structurally related leucocidin subunits, consistent with recognition of conserved epitopes. These findings also provide the first evidence of a relationship between the reactivity of antistaphylococcal circulating memory B cells and serum antibody levels. In general, infection was not associated with a global defect in B-cell memory forS. aureussecreted factors, and responses were highly dominated by cross-reactivity to structurally related exotoxins, which arguably may alone be suboptimal in providing host defenses. Our studies illuminate aspects of theS. aureus-host relationship that may better inform strategies for the development of an effective protective vaccine.

scholarly journals Gene Dose–Dependent Maturation and Receptor Editing of B Cells Expressing Immunoglobulin (Ig)g1 or Igm/Igg1 Tail Antigen Receptors

2000 ◽  
Vol 191 (6) ◽  
pp. 1031-1044 ◽  
Author(s):  
Sarah L. Pogue ◽  
Christopher C. Goodnow
Keyword(s):  
B Cells ◽  
Transgenic Mice ◽  
B Cell ◽  
Copy Number ◽  
Memory B Cells ◽  
Mouse Strains ◽  
Allelic Exclusion ◽  
Antigen Receptors ◽  
Cytoplasmic Domains ◽  
Transgene Copy Number

Conserved differences between the transmembrane and cytoplasmic domains of membrane immunoglobulin (Ig)M and IgG may alter the function of antigen receptors on naive versus memory B cells. Here, we compare the ability of these domains to signal B cell allelic exclusion and maturation in transgenic mice. A lysozyme-binding antibody was expressed in parallel sets of mice as IgM, IgG1, or a chimeric receptor with IgM extracellular domains and transmembrane/cytoplasmic domains of IgG1. Like IgM, the IgG1 or chimeric IgM/G receptors triggered heavy chain allelic exclusion and supported development of mature CD21+ B cells. Many of the IgG or IgM/G B cells became CD21high and downregulated their IgG and IgM/G receptors spontaneously, resembling memory B cells and B cells with mutations that exaggerate B cell antigen receptor signaling. Unlike IgM-transgenic mice, “edited” B cells that carry non–hen egg lysozyme binding receptors preferentially accumulated in IgG and IgM/G mice. This was most extreme in lines with the highest transgene copy number and diminished in variant offspring with fewer copies. The sensitivity of B cell maturation to transgene copy number conferred by the IgG transmembrane and cytoplasmic domains may explain the diverse phenotypes found in other IgG-transgenic mouse strains and may reflect exaggerated signaling.

scholarly journals Antigen-Specific B Cell Memory

2000 ◽  
Vol 191 (7) ◽  
pp. 1149-1166 ◽  
Author(s):  
Louise J. McHeyzer-Williams ◽  
Melinda Cool ◽  
Michael G. McHeyzer-Williams
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Memory B Cells ◽  
Cell Memory ◽  
Specific Memory ◽  
B Cell Memory ◽  
Cellular Components

The mechanisms that regulate B cell memory and the rapid recall response to antigen remain poorly defined. This study focuses on the rapid expression of B cell memory upon antigen recall in vivo, and the replenishment of quiescent B cell memory that follows. Based on expression of CD138 and B220, we reveal a unique and major subtype of antigen-specific memory B cells (B220−CD138−) that are distinct from antibody-secreting B cells (B220+/−CD138+) and B220+CD138− memory B cells. These nonsecreting somatically mutated B220− memory responders rapidly dominate the splenic response and comprise >95% of antigen-specific memory B cells that migrate to the bone marrow. By day 42 after recall, the predominant quiescent memory B cell population in the spleen (75–85%) and the bone marrow (>95%) expresses the B220− phenotype. Upon adoptive transfer, B220− memory B cells proliferate to a lesser degree but produce greater amounts of antibody than their B220+ counterparts. The pattern of cellular differentiation after transfer indicates that B220− memory B cells act as stable self-replenishing intermediates that arise from B220+ memory B cells and produce antibody-secreting cells on rechallenge with antigen. Cell surface phenotype and Ig isotype expression divide the B220− compartment into two main subsets with distinct patterns of integrin and coreceptor expression. Thus, we identify new cellular components of B cell memory and propose a model for long-term protective immunity that is regulated by a complex balance of committed memory B cells with subspecialized immune function.

miRNA Profiling of B Cell Subsets: Specific miRNA Profile for Germinal Center B Cells with a Marked Variation Between Centroblast and Centrocytes.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1459-1459
Author(s):  
Lu Ping Tan ◽  
Miao Wang ◽  
Jan-Lukas Robertus ◽  
Rikst Nynke Schakel ◽  
Johan H Gibcus ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Germinal Center ◽  
Germinal Centers ◽  
Memory B Cells ◽  
Mirna Profile ◽  
Mantle Zone ◽  
Tissue Sections ◽  
Germinal Center B Cell ◽  
Germinal Center B Cells

Abstract MiRNAs are a new class of small RNAs, of 19–23 nucleotides that were discovered less than two decades ago. These tiny RNAs can negatively regulate genes at the post-transcriptional level by either triggering translational repression or direct cleavage of mRNAs. It has become evident that miRNAs are involved in hematopoiesis and that the aberrant expression of miRNAs may give rise to hematopoietic malignancies. The aim of our study was to characterize the miRNA profile of naïve, germinal center and memory B cells sorted from tonsils and review expression of selected miRNAs in tonsils and in B cell malignancies by miRNA in situ hybridization (ISH). Quantitative (q)RT-PCR profiling revealed that several miRNAs were elevated in germinal center B cells, including miR-17–5p, miR-106a and miR-181b. miR-150 was one of the most abundant miRNAs in all subsets, but the expression level was more than 10 fold lower in germinal center B cell as compared to the other two subsets. MiRNA ISH on tonsillar tissue sections confirmed findings from the profiling work, and at the same time depicted differences in staining intensities within germinal centers. According to miRNA ISH, expression levels of miR-17-5p, miR-106a, and miR-181b were indeed higher in germinal center B cells as compared to naïve and memory B cells in the mantle zone. Surprisingly, we also observed gradual decrease of miR-17-5p, miR-106a, and miR-181b staining from dark to light zone in the germinal centers. Moreover, miRNA ISH with a probe for miR-150 demonstrated an interesting staining pattern in lymph node tissue sections. Naïve and memory B cells located in the mantle zone showed a higher miR-150 expression as compared to most of the cells in the germinal centers. However, within the germinal centers a minority of cells showed a much stronger cytoplasmic staining in part of the blasts located specifically in the dark zone. This indicated that part of the centroblasts have a high expression level of miR-150. The level of miR-150 was surprisingly low in 22 B cell lymphoma cell lines, irrespective of germinal center or non germinal center B cell origin. This seemingly negative association of miR-150 with proliferation suggests a role in B cell growth/death. We observed an inverse expression pattern of miR-150 and Survivin in the germinal centers by miRNA ISH and immunohistochemistry. Moreover, induction of miR-150 using synthetic mature miR-150 duplex resulted in reduced Survivin expression levels. Our results suggested that aside the experimentally proven target c-Myb, Survivin may also be regulated by miR-150. In conclusion, we have revealed a unique miRNA profile of naïve, germinal center and memory B cells sorted from normal tonsils and the results were confirmed by miRNA ISH. Within the germinal centers a marked difference was observed between the light zone and the dark zone.

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 Coupled Antigen and BLIMP1 Asymmetric Division With a Large Segregation Between Daughter Cells Recapitulates the Temporal Transition From Memory B Cells to Plasma Cells and a DZ-to-LZ Ratio in the Germinal Center

2021 ◽  
Vol 12 ◽  
Author(s):  
Elena Merino Tejero ◽  
Danial Lashgari ◽  
Rodrigo García-Valiente ◽  
Jiaojiao He ◽  
Philippe A. Robert ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
Plasma Cell ◽  
Germinal Center ◽  
Plasma Cells ◽  
Germinal Centers ◽  
Memory B Cells ◽  
Plasma Cell Differentiation ◽  
Daughter Cells

Memory B cells and antibody-secreting plasma cells are generated within germinal centers during affinity maturation in which B-cell proliferation, selection, differentiation, and self-renewal play important roles. The mechanisms behind memory B cell and plasma cell differentiation in germinal centers are not well understood. However, it has been suggested that cell fate is (partially) determined by asymmetric cell division, which involves the unequal distribution of cellular components to both daughter cells. To investigate what level and/or probability of asymmetric segregation of several fate determinant molecules, such as the antigen and transcription factors (BCL6, IRF4, and BLIMP1) recapitulates the temporal switch and DZ-to-LZ ratio in the germinal center, we implemented a multiscale model that combines a core gene regulatory network for plasma cell differentiation with a model describing the cellular interactions and dynamics in the germinal center. Our simulations show that BLIMP1 driven plasma cell differentiation together with coupled asymmetric division of antigen and BLIMP1 with a large segregation between the daughter cells results in a germinal center DZ-to-LZ ratio and a temporal switch from memory B cells to plasma cells that have been observed in experiments.

BAFFR Activates PI3K/AKT Signaling in Human Naive But Not in Switched Memory B Cells Through Direct Interactions with B Cell Antigen Receptors

2021 ◽  
Author(s):  
Eirini Sevdali ◽  
Violeta Block ◽  
Marie Lataretu ◽  
Huiying Li ◽  
Cristian R. Smulski ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Akt Signaling ◽  
Memory B Cells ◽  
Antigen Receptors ◽  
Cell Antigen

scholarly journals Induction of Mucosal B-Cell Memory by Intranasal Immunization of Mice with Respiratory Syncytial Virus

2005 ◽  
Vol 12 (1) ◽  
pp. 171-179 ◽  
Author(s):  
Janine Valosky ◽  
Haruka Hishiki ◽  
Theoklis E. Zaoutis ◽  
Susan E. Coffin
Keyword(s):  
Respiratory Syncytial Virus ◽  
B Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Memory B Cells ◽  
Lymphoid Tissues ◽  
Primary Immunization ◽  
Cell Memory ◽  
B Cell Memory ◽  
Syncytial Virus

ABSTRACT The capacity of live or inactivated respiratory syncytial virus (RSV) to induce B-cell memory in respiratory-associated lymphoid tissues of mice was examined. Eight weeks after primary inoculation with either live or inactivated RSV, adult BALB/c mice were challenged with 4 × 105 PFU of RSV. Protection from viral shedding and mucosal production of RSV-specific antibodies were examined at various time points after challenge. We found that primary immunization with live, but not inactivated, RSV induced complete and durable protection upon challenge within the upper and lower respiratory tract. Also, primary immunization with live, but not inactivated, RSV enhanced the production of mucosal RSV-specific immunoglobulin A (IgA) upon challenge. Secondary mucosal IgA responses were characterized by (i) the early production of mucosal IgA by B cells that reside in organized nasal-associated lymphoid tissues, cervical lymph nodes, and bronchial lymph nodes, and (ii) the subsequent production of RSV-specific IgA by mucosal effector tissues, such as the tracheal lamina propria and lung. These findings suggest that primary infection of mice with live RSV might induce mucosal IgA-committed memory B cells. A greater understanding of the characteristics of RSA-specific mucosal memory B cells may facilitate the development of an RSV vaccine.

scholarly journals Very Low Affinity B Cells Form Germinal Centers, Become Memory B Cells, and Participate in Secondary Immune Responses When Higher Affinity Competition Is Reduced

2002 ◽  
Vol 195 (9) ◽  
pp. 1215-1221 ◽  
Author(s):  
Joseph M. Dal Porto ◽  
Ann M. Haberman ◽  
Garnett Kelsoe ◽  
Mark J. Shlomchik
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
B Cell ◽  
B Lymphocytes ◽  
Germinal Center ◽  
Germinal Centers ◽  
Association Constants ◽  
Memory B Cells ◽  
B Cell Antigen Receptor ◽  
The Relationship

To understand the relationship between the affinity of the B cell antigen receptor (BCR) and the immune response to antigen, two lines of immunoglobulin H chain transgenic (Tg) mice were created. H50Gμa and T1(V23)μa mice express μ H chain transgenes that associate with the λ1 L chains to bind the (4-hydroxy-3-nitrophenyl)acetyl hapten with association constants (Kas) of only 1.2 × 105 M−1 and 3 × 104 M−1, respectively. Both lines mounted substantial antibody-forming cell (AFC) and germinal center (GC) responses. H50Gμa Tg mice also generated memory B cells. T1(V23)μa B cells formed AFC and GCs, but were largely replaced in late GCs by antigen-specific cells that express endogenous BCRs. Thus, B lymphocytes carrying BCRs with affinities previously thought to be irrelevant in specific immune responses are in fact capable of complete T cell–dependent immune responses when relieved of substantial competition from other B cells. The failure to observe such B cells normally in late primary responses and in memory B cell populations is the result of competition, rather than an intrinsic inability of low affinity B cells.

scholarly journals 44 Detection of memory B cells cross-reactive against polymorphic malaria antigens using a multiplex FluoroSpot assay

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A51-A51
Author(s):  
David Spezzano ◽  
Peter Jahnmatz ◽  
Evan Johnson
Keyword(s):  
B Cells ◽  
B Cell ◽  
Vaccine Development ◽  
Merozoite Surface Protein ◽  
Cross Reactivity ◽  
Memory B Cells ◽  
University Hospital ◽  
Antigen Specificity ◽  
Preliminary Results ◽  
Merozoite Antigens

BackgroundAntigenic diversity of the malaria parasite Plasmodium falciparum is a major challenge for vaccine development. Identifying cross-reactive antibodies to polymorphic antigens linked with protection, eg merozoite surface protein 2 (MSP2), could further guide vaccine design. Circulating malaria-specific antibodies are generally short-lived and analysis of memory B-cells (MBC) may therefore better reflect responses of importance for immunity. The B-cell FluoroSpot assay enables a sensitive analysis of antigen-specific B cells, in addition, it allows also for analysis of cross-reactivity displayed by single B cells.MethodsPatients treated for P. falciparum malaria at Karolinska University Hospital in Stockholm Sweden were followed prospectively with repeated sampling over one year. PBMCs were analyzed using a B-cell FluoroSpot assay including P. falciparum antigens MSP-1(19), MSP-3, AMA-1 and different variants of MSP2. The gene coding for the polymorphic region of MSP-2 from the patient‘s own parasite was amplified, sequenced and recombinantly expressed together with a peptide tag that enabled detection in the FluoroSpot assay. Combinations of MSP2 variants were tested for homologous and heterologous responses.ResultsPreliminary results show that the FluoroSpot assay was able to simultaneously detect single MBCs specific against the different merozoite antigens in the same well including either one of the antigen variant of MSP-2 in patients with single or repeated exposure to malaria (figure 1). Cross-reactivity displayed by single B cells to different MSP2 antigens was detected in variants within the two respective allelic families FC27 and 3D7 but not between allelic families. Further analyses are ongoing involving additional antigens as well as individuals with different degree of pre-existing immunity.Abstract 44 Figure 1Detection of memory B cells cross-reactive against polymorph. Detection of memory B cells cross-reactive against polymorphic malaria antigens using a multiplex FluoroSpot assayConclusionsPreliminary results suggest that this novel multiplex B-cell FluoroSpot assay could be a powerful tool to analyze antigen-specificity and antibody cross-reactivity to polymorphic merozoite antigens and its association with previous exposure and immunity.

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