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 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 Impaired Antibody-mediated Protection and Defective IgA B-Cell Memory in Experimental Infection of Adults with Respiratory Syncytial Virus

2015 ◽  
Vol 191 (9) ◽  
pp. 1040-1049 ◽  
Author(s):  
Maximillian S. Habibi ◽  
Agnieszka Jozwik ◽  
Spyridon Makris ◽  
Jake Dunning ◽  
Allan Paras ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
B Cell ◽  
Experimental Infection ◽  
Cell Memory ◽  
B Cell Memory ◽  
Syncytial Virus

scholarly journals Shared B cell memory to coronaviruses and other pathogens varies in human age groups and tissues

2020 ◽  
Author(s):  
Fan Yang ◽  
Sandra C. A. Nielsen ◽  
Ramona A. Hoh ◽  
Ji-Yeun Lee ◽  
Tho D. Pham ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Clonal Evolution ◽  
Age Groups ◽  
Immune Memory ◽  
Lymphoid Tissues ◽  
Specific Class ◽  
Cell Memory ◽  
Age Related ◽  
B Cell Memory

AbstractVaccination and infection promote the formation, tissue distribution, and clonal evolution of B cells encoding humoral immune memory. We evaluated convergent antigen-specific antibody genes of similar sequences shared between individuals in pediatric and adult blood, and deceased organ donor tissues. B cell memory varied for different pathogens. Polysaccharide antigen-specific clones were not exclusive to the spleen. Adults’ convergent clones often express mutated IgM or IgD in blood and are class-switched in lymphoid tissues; in contrast, children have abundant class-switched convergent clones in blood. Consistent with serological reports, pre-pandemic children had class-switched convergent clones to SARS-CoV-2, enriched in cross-reactive clones for seasonal coronaviruses, while adults showed few such clones in blood or lymphoid tissues. These results extend age-related and anatomical mapping of human humoral pathogen-specific immunity.One Sentence SummaryChildren have elevated frequencies of pathogen-specific class-switched memory B cells, including SARS-CoV-2-binding clones.

scholarly journals Modification of the Respiratory Syncytial Virus F Protein in Virus-Like Particles Impacts Generation of B Cell Memory

2014 ◽  
Vol 88 (17) ◽  
pp. 10165-10176 ◽  
Author(s):  
M. R. Schmidt ◽  
L. W. McGinnes-Cullen ◽  
S. A. Kenward ◽  
K. N. Willems ◽  
R. T. Woodland ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
B Cell ◽  
Cell Memory ◽  
F Protein ◽  
Virus Like Particles ◽  
B Cell Memory ◽  
Syncytial Virus

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 Antiviral Protection and Germinal Center Formation, But Impaired B Cell Memory in the Absence of CD19

1998 ◽  
Vol 188 (1) ◽  
pp. 145-155 ◽  
Author(s):  
Thomas Fehr ◽  
Robert C. Rickert ◽  
Bernhard Odermatt ◽  
Jürgen Roes ◽  
Klaus Rajewsky ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Antibody Responses ◽  
B Cell Activation ◽  
Protein Antigens ◽  
Cell Memory ◽  
B Cell Memory

Coligation of CD19, a molecule expressed during all stages of B cell development except plasmacytes, lowers the threshold for B cell activation with anti-IgM by a factor of 100. The cytoplasmic tail of CD19 contains nine tyrosine residues as possible phosphorylation sites and is postulated to function as the signal transducing element for complement receptor (CR)2. Generation and analysis of CD19 gene–targeted mice revealed that T cell–dependent (TD) antibody responses to proteinaceous antigens were impaired, whereas those to T cell–independent (TI) type 2 antigens were normal or even augmented. These results are compatible with earlier complement depletion studies and the postulated function of CD19. To analyze the role of CD19 in antiviral antibody responses, we immunized CD19−/− mice with viral antigens of TI-1, TI-2, and TD type. The effect of CD19 on TI responses was more dependent on antigen dose and replicative capacity than on antigen type. CR blocking experiments confirmed the role of CD19 as B cell signal transducer for complement. In contrast to immunization with protein antigens, infection of CD19−/− mice with replicating virus led to generation of specific germinal centers, which persisted for >100 d, whereas maintenance of memory antibody titers as well as circulating memory B cells was fully dependent on CD19. Thus, our study confirms a costimulatory role of CD19 on B cells under limiting antigen conditions and indicates an important role for B cell memory.

Sphingosine 1-phosphate regulates peritoneal B-cell trafficking for subsequent intestinal IgA production

Blood ◽  
2007 ◽  
Vol 109 (9) ◽  
pp. 3749-3756 ◽  
Author(s):  
Jun Kunisawa ◽  
Yosuke Kurashima ◽  
Masashi Gohda ◽  
Morio Higuchi ◽  
Izumi Ishikawa ◽  
...  
Keyword(s):  
B Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Antibody Production ◽  
Pivotal Role ◽  
Secretory Iga ◽  
Lymphoid Tissues ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor ◽  
Iga Production

AbstractSphingosine 1-phosphate (S1P) is known to play a pivotal role in the regulation of lymphocyte emigration from organized lymphoid tissues such as the peripheral lymph nodes and thymus, but its immunologic role in unorganized and diffused tissues remains to be elucidated. Here we show that the trafficking of peritoneal B cells is principally regulated by S1P. All peritoneal B cells including B1a, B1b, and B2 B cells express comparable levels of the type 1 S1P receptor. Thus, treatment with FTY720, an S1P receptor modulator, caused the rapid disappearance of peritoneal B cells by inhibiting both their emigration from parathymic lymph nodes and their recirculation from the blood into the peritoneal cavity without affecting their progenitor populations. These changes did not affect natural plasma antibody production or phosphorylcholine (PC)–specific antibody production in serum after peritoneal immunization with heat-killed Streptococcal pneumoniae (R36A). However, FTY720 dramatically reduced peritoneal B cell-derived natural intestinal secretory IgA production without affecting the expression of J-chain and polyimmunoglobulin receptors. Additionally, FTY720 impaired the generation of PC-specific fecal IgA responses after oral immunization with R36A. These findings point to a pivotal role for S1P in connecting peritoneal B cells with intestinal B-cell immunity.

scholarly journals Differential effects of fingolimod on B-cell populations in multiple sclerosis

2014 ◽  
Vol 20 (10) ◽  
pp. 1371-1380 ◽  
Author(s):  
Masakazu Nakamura ◽  
Takako Matsuoka ◽  
Norio Chihara ◽  
Sachiko Miyake ◽  
Wakiro Sato ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
B Cells ◽  
B Cell ◽  
Mononuclear Cells ◽  
Memory B Cells ◽  
Lymphoid Cells ◽  
Oral Drug ◽  
Cell Populations ◽  
Lymphoid Tissues ◽  
Ki 67

Background: Fingolimod is an oral drug approved for multiple sclerosis (MS) with an ability to trap central memory T cells in secondary lymphoid tissues; however, its variable effectiveness in individual patients indicates the need to evaluate its effects on other lymphoid cells. Objective: To clarify the effects of fingolimod on B-cell populations in patients with MS. Methods: We analysed blood samples from 9 fingolimod-treated and 19 control patients with MS by flow cytometry, to determine the frequencies and activation states of naive B cells, memory B cells, and plasmablasts. Results: The frequencies of each B-cell population in peripheral blood mononuclear cells (PBMC) were greatly reduced 2 weeks after starting fingolimod treatment. Detailed analysis revealed a significant reduction in activated memory B cells (CD38int-high), particularly those expressing Ki-67, a marker of cell proliferation. Also, we noted an increased proportion of activated plasmablasts (CD138+) among whole plasmablasts, in the patients treated with fingolimod. Conclusions: The marked reduction of Ki-67+ memory B cells may be directly linked with the effectiveness of fingolimod in treating MS. In contrast, the relative resistance of CD138+ plasmablasts to fingolimod may be of relevance for understanding the differential effectiveness of fingolimod in individual patients.

scholarly journals Rituximab efficiently depletes B cells in lung tumors and normal lung tissue

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 38 ◽  
Author(s):  
Albane Joly-Battaglini ◽  
Clara Hammarström ◽  
Branislava Stankovic ◽  
Henrik Aamodt ◽  
Johan Stjärne ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Lung Tissue ◽  
Lung Tumor ◽  
B Cell Lymphoma ◽  
Normal Lung Tissue ◽  
Normal Lung ◽  
Lymphoid Tissues

Rituximab is a monoclonal antibody that targets the CD20 B-cell-specific antigen and is widely used as therapy for B-cell lymphoma. Since rituximab depletes both malignant and normal B cells, it is increasingly being used to treat various conditions in which normal B cells have a pathogenic role, such as rheumatoid arthritis and multiple sclerosis. It is well-established that rituximab efficiently eliminates B cells in blood, lymph nodes, and spleen. In contrast, the effect of rituximab in non-lymphoid tissues remains poorly documented and is debated. Here, we report a rheumatoid arthritis patient who was treated with rituximab before receiving thoracic surgery for non-small cell lung cancer. Using flow cytometry and immunohistochemistry, we show that rituximab efficiently depleted CD20-positive B cells in a primary lung tumor, in lung-associated lymph nodes, and in normal lung tissue. We conclude that rituximab may be very efficient at depleting normal B cells in the lungs. This property of rituximab may potentially be exploited for the treatment of conditions in which pathogenic B cells reside in the lungs. On the other hand, the clearance of lung B cells may provide an explanation for the rare cases of severe non-infectious pulmonary toxicity of rituximab.

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