scholarly journals Analysis of the heterogeneity of the BCR H-CDR3 repertoire in the bone marrow and spleen of 3-, 12-, and 20-month old mice

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Lina Ma ◽  
Xinxin Tao ◽  
Xiaoyan He ◽  
Peng Wang ◽  
Long Ma ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Memory B Cells ◽  
Aged Mice ◽  
Cell Immunity ◽  
Different Ages ◽  
Repertoire Diversity ◽  
Old Mice ◽  
Peripheral B Cells

AbstractThe number of central and peripheral B cells and their responsiveness are decreased in aged mice. The diversity of mice central and peripheral B cell repertoires with increasing age has not been elucidated. In this study, we demonstrated that there were significant differences in the usage of some V, D, and J genes in the BCR H-CDR3 repertoire of bone marrow B cells, spleen B cells and spleen memory B cells in 3-, 12-, and 20-month-old mice. In the productive, pseudogene, and out-of-frame sequences, bone marrow B cells had significant differences in 5′J trimming with age; peripheral spleen B cells and memory B cells had significant differences in N1 insertion, N2 insertion, P5’D insertion, and 5’D trimming with age. The BCR H-CDR3 repertoire diversity of mice bone marrow B cells, spleen B cells and spleen memory B cells decreased with increasing age. The proportion of overlap in bone marrow and spleen B cells, but not spleen memory B cells, of mice at different ages was lower at 3 months than at 12 and 20 months. This study is the first to report the homogeneity and heterogeneity of the CDR3 repertoire of central and peripheral B cells change as mice age, to further investigation of the decline and response of B cell immunity in young/middle/old-aged mice.

scholarly journals Analysis of the heterogeneity of the BCR H-CDR3 repertoire in the bone marrow and spleen of 3-, 12-, and 20-month old mice 

2020 ◽  
Author(s):  
Lina Ma ◽  
Xinsheng Yao ◽  
Tao Xinxin ◽  
He Xiaoyan ◽  
Wang Peng ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Memory B Cells ◽  
Mouse Bone Marrow ◽  
Aged Mice ◽  
Cell Immunity ◽  
Repertoire Diversity ◽  
Old Mice ◽  
Peripheral B Cells

Abstract The number of central and peripheral B cells and their responsiveness are decreased in aged mice. The diversity of mouse central and peripheral B cell repertoires with increasing age has not been elucidated. In this study, we demonstrated that there were significant differences in the usage of some V, D, and J genes in the BCR H-CDR3 repertoire of bone marrow B cells, spleen B cells and spleen memory B cells in 3-, 12-, and 20-month-old mice. In the productive, pseudogene, and out-of-frame sequences, bone marrow B cells had significant differences in 5′J trimming with age; peripheral spleen B cells and memory B cells had significant differences in N1 insertion, N2 insertion, P5'D insertion, and 5'D trimming with age. The BCR H-CDR3 repertoire diversity of mouse bone marrow B cells, spleen B cells and spleen memory B cells decreased with increasing age. The proportion of overlap in bone marrow and spleen B cells, but not spleen memory B cells, of mice at different ages was lower at 3 months than at 12 and 20 months. This study is the first to report the homogeneity and heterogeneity of the CDR3 repertoire of central and peripheral B cells change as mice age, to further investigation of the decline and response of B cell immunity in young/middle/old-aged mice.

scholarly journals Analysis of the heterogeneity of the BCR H-CDR3 repertoire in the bone marrow and spleen of 3-,12-,and20-month old mice

2020 ◽  
Author(s):  
Lina Ma ◽  
Xinsheng Yao
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Memory B Cells ◽  
Mouse Bone Marrow ◽  
Aged Mice ◽  
Cell Immunity ◽  
Different Ages ◽  
Old Mice ◽  
Peripheral B Cells

Abstract The number of central and peripheral B cells and their responsiveness are decreased in agedmice. The diversity of mouse central and peripheral B cell repertoires with increasing age has notbeen elucidated. In this study, we demonstrated that there were significant differences in theusage of some V, D, and J genes in the BCR H-CDR3 repertoire of bone marrow B cells, spleen Bcells and spleen memory B cells in 3-, 12-, and 20-month-old mice. In the productive, pseudogene,and out-of-frame sequences, bone marrow B cells had significant differences in 5′J trimmingwith age; peripheral spleen B cells and memory B cells had significant differences in N1 insertion,N2 insertion, P5'D insertion, and 5'D trimming with age. The BCR H-CDR3 repertoire diversityof mouse bone marrow B cells, spleen B cells and spleen memory B cells decreased withincreasing age. The proportion of overlap in bone marrow and spleen B cells, but not spleenmemory B cells, of mice at different ages was lower at 3 months than at 12 and 20 months.Thisstudy is the first to report the homogeneity and heterogeneity of the CDR3 repertoire of centraland peripheral B cells change as mice age , to further investigation of the decline and response ofB cell immunity in young/middle/old-aged mice.

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.

Vaccine-elicited CD4 T cells prevent the deletion of antiviral B cells in chronic infection

2021 ◽  
Vol 118 (46) ◽  
pp. e2108157118
Author(s):  
Kerstin Narr ◽  
Yusuf I. Ertuna ◽  
Benedict Fallet ◽  
Karen Cornille ◽  
Mirela Dimitrova ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cd4 T Cells ◽  
Memory B Cells ◽  
Type I ◽  
Clonal Deletion ◽  
Cell Immunity ◽  
B Cell Immunity

Chronic viral infections subvert protective B cell immunity. An early type I interferon (IFN-I)–driven bias to short-lived plasmablast differentiation leads to clonal deletion, so-called “decimation,” of antiviral memory B cells. Therefore, prophylactic countermeasures against decimation remain an unmet need. We show that vaccination-induced CD4 T cells prevented the decimation of naïve and memory B cells in chronically lymphocytic choriomeningitis virus (LCMV)-infected mice. Although these B cell responses were largely T independent when IFN-I was blocked, preexisting T help assured their sustainability under conditions of IFN-I–driven inflammation by instructing a germinal center B cell transcriptional program. Prevention of decimation depended on T cell–intrinsic Bcl6 and Tfh progeny formation. Antigen presentation by B cells, interactions with antigen-specific T helper cells, and costimulation by CD40 and ICOS were also required. Importantly, B cell–mediated virus control averted Th1-driven immunopathology in LCMV-challenged animals with preexisting CD4 T cell immunity. Our findings show that vaccination-induced Tfh cells represent a cornerstone of effective B cell immunity to chronic virus challenge, pointing the way toward more effective B cell–based vaccination against persistent viral diseases.

Differential expression of GL7 activation antigen on bone marrow B cell subpopulations and peripheral B cells

2001 ◽  
Vol 78 (2) ◽  
pp. 89-96 ◽  
Author(s):  
László Cervenak ◽  
Attila Magyar ◽  
Roberta Boja ◽  
Glória László
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Differential Expression ◽  
Cell Subpopulations ◽  
Activation Antigen ◽  
Peripheral B Cells

scholarly journals Long‐term ethanol uptake in mice results in loss of peripheral B cells without affecting B cell production in the bone marrow

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Lorraine Tunink Tygrett ◽  
Ruth A. Coleman ◽  
Robert T. Cook ◽  
Thomas J. Waldschmidt
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Cell Production ◽  
Peripheral B Cells

scholarly journals IL-21 regulates germinal center B cell differentiation and proliferation through a B cell–intrinsic mechanism

2010 ◽  
Vol 207 (2) ◽  
pp. 365-378 ◽  
Author(s):  
Dimitra Zotos ◽  
Jonathan M. Coquet ◽  
Yang Zhang ◽  
Amanda Light ◽  
Kathy D'Costa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
Affinity Maturation ◽  
Memory B Cells ◽  
Target Cells ◽  
B Cell Differentiation ◽  
Follicular Helper

Germinal centers (GCs) are sites of B cell proliferation, somatic hypermutation, and selection of variants with improved affinity for antigen. Long-lived memory B cells and plasma cells are also generated in GCs, although how B cell differentiation in GCs is regulated is unclear. IL-21, secreted by T follicular helper cells, is important for adaptive immune responses, although there are conflicting reports on its target cells and mode of action in vivo. We show that the absence of IL-21 signaling profoundly affects the B cell response to protein antigen, reducing splenic and bone marrow plasma cell formation and GC persistence and function, influencing their proliferation, transition into memory B cells, and affinity maturation. Using bone marrow chimeras, we show that these activities are primarily a result of CD3-expressing cells producing IL-21 that acts directly on B cells. Molecularly, IL-21 maintains expression of Bcl-6 in GC B cells. The absence of IL-21 or IL-21 receptor does not abrogate the appearance of T cells in GCs or the appearance of CD4 T cells with a follicular helper phenotype. IL-21 thus controls fate choices of GC B cells directly.

scholarly journals Variation of B cell subsets with age in healthy Malawians

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254320
Author(s):  
Wilson L. Mandala ◽  
Herbert Longwe
Keyword(s):  
B Cells ◽  
B Cell ◽  
Lymphocyte Subsets ◽  
Venous Blood ◽  
Memory B Cells ◽  
Age Group ◽  
Blood Samples ◽  
Opposite Trend ◽  
Different Ages ◽  
B Cell Subsets

Although a number of previous studies have shown that different lymphocyte subsets, including B cells, vary with age, how different B cell subsets vary with age in Malawian population has not been shown before. We recruited Malawian participants of different ages and analyzed their venous blood samples for different B cell subsets. We found that both percentage and absolute counts of B cells varied with age peaking in the 7 to 12 months age group. Proportion of naïve B cells was highest in neonates and decreased with age whereas the percentage of memory B cells was lowest in neonates and increased with age. When we zeroed in on the age band within which the proportion of B cells was highest, both classical and activated memory B cells increased with age and the naïve followed the opposite trend. These results provide additional knowledge in our understanding of the dynamics of B cell subsets in individuals of a specific ethnicity as they age.

scholarly journals S protein-reactive IgG and memory B cell production after human SARS-CoV-2 infection includes broad reactivity to the S2 subunit

2020 ◽  
Author(s):  
Phuong Nguyen-Contant ◽  
A. Karim Embong ◽  
Preshetha Kanagaiah ◽  
Francisco A. Chaves ◽  
Hongmei Yang ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Receptor Binding ◽  
Memory B Cells ◽  
Binding Domain ◽  
The Novel ◽  
Receptor Binding Domain ◽  
S Protein ◽  
Cell Immunity ◽  
Antibody Levels

ABSTRACTThe high susceptibility of humans to SARS-CoV-2 infection, the cause of COVID-19, reflects the novelty of the virus and limited preexisting B cell immunity. IgG against the SARS-CoV-2 spike (S) protein, which carries the novel receptor binding domain (RBD), is absent or at low levels in unexposed individuals. To better understand the B cell response to SARS-CoV-2 infection, we asked whether virus-reactive memory B cells (MBCs) were present in unexposed subjects and whether MBC generation accompanied virus-specific IgG production in infected subjects. We analyzed sera and PBMCs from non-SARS-CoV-2-exposed healthy donors and COVID-19 convalescent subjects. Serum IgG levels specific for SARS-CoV-2 proteins (S, including the RBD and S2 subunit, and nucleocapsid [N]) and non-SARS-CoV-2 proteins were related to measurements of circulating IgG MBCs. Anti-RBD IgG was absent in unexposed subjects. Most unexposed subjects had anti-S2 IgG and a minority had anti-N IgG, but IgG MBCs with these specificities were not detected, perhaps reflecting low frequencies. Convalescent subjects had high levels of IgG against the RBD, S2, and N, together with large populations of RBD- and S2-reactive IgG MBCs. Notably, IgG titers against the S protein of the human coronavirus OC43 in convalescent subjects were higher than in unexposed subjects and correlated strongly with anti-S2 titers. Our findings indicate cross-reactive B cell responses against the S2 subunit that might enhance broad coronavirus protection. Importantly, our demonstration of MBC induction by SARS-CoV-2 infection suggests that a durable form of B cell immunity is maintained even if circulating antibody levels wane.IMPORTANCERecent rapid worldwide spread of SARS-CoV-2 has established a pandemic of potentially serious disease in the highly susceptible human population. Key questions are whether humans have preexisting immune memory that provides some protection against SARS-CoV-2 and whether SARS-CoV-2 infection generates lasting immune protection against reinfection. Our analysis focused on pre- and post-infection IgG and IgG memory B cells (MBCs) reactive to SARS-CoV-2 proteins. Most importantly, we demonstrate that infection generates both IgG and IgG MBCs against the novel receptor binding domain and the conserved S2 subunit of the SARS-CoV-2 spike protein. Thus, even if antibody levels wane, long-lived MBCs remain to mediate rapid antibody production. Our study also suggests that SARS-CoV-2 infection strengthens preexisting broad coronavirus protection through S2-reactive antibody and MBC formation.

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