scholarly journals A longitudinal study of plasma BAFF levels in mothers and their infants in Uganda, and correlations with subsets of B cells

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245431
Author(s):  
Caroline Rönnberg ◽  
Allan Lugaajju ◽  
Anna Nyman ◽  
Ulf Hammar ◽  
Matteo Bottai ◽  
...  
Keyword(s):  
At Risk ◽  
B Cells ◽  
B Cell ◽  
Adaptive Immune Response ◽  
Memory B Cells ◽  
Natural Immunity ◽  
B Cell Memory ◽  
New Information ◽  
Life Threatening ◽  
B Cell Homeostasis

Malaria is a potentially life-threatening disease with approximately half of the world’s population at risk. Young children and pregnant women are hit hardest by the disease. B cells and antibodies are part of an adaptive immune response protecting individuals continuously exposed to the parasite. An infection with Plasmodium falciparum can cause dysregulation of B cell homeostasis, while antibodies are known to be key in controlling symptoms and parasitemia. BAFF is an instrumental cytokine for the development and maintenance of B cells. Pregnancy alters the immune status and renders previously clinically immune women at risk of severe malaria, potentially due to altered B cell responses associated with changes in BAFF levels. In this prospective study, we investigated the levels of BAFF in a malaria-endemic area in mothers and their infants from birth up to 9 months. We found that BAFF-levels are significantly higher in infants than in mothers. BAFF is highest in cord blood and then drops rapidly, but remains significantly higher in infants compared to mothers even at 9 months of age. We further correlated BAFF levels to P. falciparum-specific antibody levels and B cell frequencies and found a negative correlation between BAFF and both P. falciparum-specific and total proportions of IgG+ memory B cells, as well as CD27− memory B cells, indicating that exposure to both malaria and other diseases affect the development of B-cell memory and that BAFF plays a part in this. In conclusion, we have provided new information on how natural immunity against malaria is formed.

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.

scholarly journals Absence of surface IgD does not impair naive B cell homeostasis and memory B cell formation in humans

2018 ◽  
Author(s):  
J. Nechvatalova ◽  
S.J.W. Bartol ◽  
Z. Chovancova ◽  
L. Boon ◽  
M. Vlkova ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Genetic Defect ◽  
Memory B Cells ◽  
Cell Homeostasis ◽  
Human B Cells ◽  
B Cell Homeostasis

One Sentence SummaryHuman B cells with a genetic defect in IGHD develop normally in vivo, and do not have a competitive disadvantage to IgD-expressing B cells for developing into memory B cells.AbstractSurface immunoglobulin D (IgD) is co-expressed with IgM on naive mature B cells. Still, the role of surface IgD remains enigmatic even 50 years after its initial discovery. We here examined the in vivo role of surface IgD in human B-cell homeostasis and antibody responses in four individuals with heterozygous nonsense mutations in IGHD. All IGHD heterozygous individuals had normal numbers of B cells and serum immunoglobulins, and did not show signs of immunodeficiency or immune dysregulation. IgD+ and IgD– naive mature B cells were present in equal numbers and showed similar immunophenotypes, except for decreased expression of CD79b in the IgD– subset. Furthermore, both IgD+ and IgD– naive mature B cells had normal replication histories, similar capacities to differentiate into plasma cells upon in vitro stimulation, and Ig switched memory B cells showed similar levels of somatic hypermutations. Thus human B cells lacking IgD expression develop normally and generate immunological memory in vivo, suggesting that surface IgD might function more restricted in regulating of B-cell activation to specific antigenic structures.

BAFF enhances chemotaxis of primary human B cells: a particular synergy between BAFF and CXCL13 on memory B cells

Blood ◽  
2008 ◽  
Vol 111 (5) ◽  
pp. 2744-2754 ◽  
Author(s):  
Gamal Badr ◽  
Gwenoline Borhis ◽  
Eric A. Lefevre ◽  
Nada Chaoul ◽  
Frederique Deshayes ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Stromal Cells ◽  
B Lymphocyte ◽  
Memory B Cells ◽  
Follicular Dendritic Cells ◽  
Human B Cells ◽  
Lymphocyte Survival ◽  
B Cell Homeostasis ◽  
Cell Chemotaxis

B-cell–activating factor of the TNF family, (BAFF), and a proliferation-inducing ligand (APRIL) regulate B-lymphocyte survival and activation. We report that BAFF, but not APRIL, increased the chemotactic response of primary human B cells to CCL21, CXCL12, and CXCL13. The BAFF-induced increase in B-cell chemotaxis was totally abolished by blockade of BAFF-R and was strongly dependent on the activation of PI3K/AKT, NF-κB, and p38MAPK pathways. BAFF had similar effects on the chemotaxis of naive and memory B cells in response to CCL21 but increased more strongly that of memory B cells to CXCL13 than that of naive B cells. Our findings indicate a previously unreported role for the BAFF/BAFF-R pair in mature B-cell chemotaxis. The synergy between CXCL13 and BAFF produced by stromal cells and follicular dendritic cells may have important implications for B-cell homeostasis, the development of normal B-cell areas, and for the formation of germinal center–like follicles that may be observed in various autoimmune diseases.

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 B Cell Receptor Repertoire Analysis in Malaria-Naive and Malaria-Experienced Individuals Reveals Unique Characteristics of Atypical Memory B Cells

mSphere ◽  
2021 ◽  
Author(s):  
Ashley E. Braddom ◽  
Sebastiaan Bol ◽  
S. Jake Gonzales ◽  
Raphael A. Reyes ◽  
Kenneth Musinguzi ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Receptor ◽  
Memory B Cells ◽  
B Cell Receptor ◽  
Receptor Repertoire ◽  
Repertoire Analysis ◽  
B Cell Memory ◽  
Cell Receptor Repertoire ◽  
Children Under 5

Malaria, caused by Plasmodium parasites, still contributes to a high global burden of disease, mainly in children under 5 years of age. Chronic and recurrent Plasmodium infections affect the development of B cell memory against the parasite and promote the accumulation of atypical memory B cells (atMBCs), which have an unclear function in the immune response.

scholarly journals The human spleen is a major reservoir for long-lived vaccinia virus–specific memory B cells

Blood ◽  
2008 ◽  
Vol 111 (9) ◽  
pp. 4653-4659 ◽  
Author(s):  
Maria Mamani-Matsuda ◽  
Antonio Cosma ◽  
Sandra Weller ◽  
Ahmad Faili ◽  
Caroline Staib ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
Vaccinia Virus ◽  
B Cell ◽  
Plasma Cells ◽  
Memory B Cells ◽  
Homeostatic Regulation ◽  
Human Spleen ◽  
Specific Memory ◽  
B Cell Memory

Abstract The fact that you can vaccinate a child at 5 years of age and find lymphoid B cells and antibodies specific for this vaccination 70 years later remains an immunologic enigma. It has never been determined how these long-lived memory B cells are maintained and whether they are protected by storage in a special niche. We report that, whereas blood and spleen compartments present similar frequencies of IgG+ cells, antismallpox memory B cells are specifically enriched in the spleen where they account for 0.24% of all IgG+ cells (ie, 10-20 million cells) more than 30 years after vaccination. They represent, in contrast, only 0.07% of circulating IgG+ B cells in blood (ie, 50-100 000 cells). An analysis of patients either splenectomized or rituximab-treated confirmed that the spleen is a major reservoir for long-lived memory B cells. No significant correlation was observed between the abundance of these cells in blood and serum titers of antivaccinia virus antibodies in this study, including in the contrasted cases of B cell– depleting treatments. Altogether, these data provide evidence that in humans, the two arms of B-cell memory—long-lived memory B cells and plasma cells—have specific anatomic distributions—spleen and bone marrow—and homeostatic regulation.

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 Induction of Mucosal B-Cell Memory by Intramuscular Inoculation of Mice with Rotavirus

1998 ◽  
Vol 72 (4) ◽  
pp. 3479-3483 ◽  
Author(s):  
Susan E. Coffin ◽  
Paul A. Offit
Keyword(s):  
B Cells ◽  
B Cell ◽  
Immunoglobulin A ◽  
Memory B Cells ◽  
Heterologous Host ◽  
Specific Memory ◽  
B Cell Memory ◽  
Intramuscular Inoculation ◽  
Specific Immunoglobulin ◽  
Iga Production

ABSTRACT We investigated the capacity of intramuscular (i.m.) immunization with heterologous-host rotavirus (simian strain RRV) to induce mucosal virus-specific memory B cells in mice. We found that prior i.m. immunization enhanced the magnitude of mucosal virus-specific immunoglobulin A (IgA) production but did not alter the site and timing of induction of virus-specific IgA responses after challenge.

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.

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