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

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.

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

Science ◽

10.1126/science.abf6648 ◽

2021 ◽

pp. eabf6648

Author(s):

Fan Yang ◽

Sandra C. A. Nielsen ◽

Ramona A. Hoh ◽

Katharina Röltgen ◽

Oliver Fabian Wirz ◽

...

Keyword(s):

B Cell ◽

Clonal Evolution ◽

Age Groups ◽

Organ Donor ◽

Cross Reactivity ◽

Immune Memory ◽

Lymphoid Tissues ◽

Cell Memory ◽

Humoral Immune ◽

B Cell Memory

Vaccination and infection promote the formation, tissue distribution, and clonal evolution of B cells, which encode 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 had higher clone frequencies and greater class-switching in lymphoid tissues than blood, while pediatric blood had abundant class-switched convergent clones. Consistent with reported serology, pre-pandemic children had class-switched convergent clones to SARS-CoV-2 with weak cross-reactivity to other coronaviruses, while adult blood or tissues showed few such clones. The results highlight the prominence of early childhood B cell clonal expansions and cross-reactivity for future responses to novel pathogens.

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

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.12.1.171-179.2005 ◽

2005 ◽

Vol 12 (1) ◽

pp. 171-179 ◽

Cited By ~ 19

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.

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

Journal of Experimental Medicine ◽

10.1084/jem.188.1.145 ◽

1998 ◽

Vol 188 (1) ◽

pp. 145-155 ◽

Cited By ~ 49

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.

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Antigen-Specific B Cell Memory

Journal of Experimental Medicine ◽

10.1084/jem.191.7.1149 ◽

2000 ◽

Vol 191 (7) ◽

pp. 1149-1166 ◽

Cited By ~ 135

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.

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Faculty Opinions recommendation of Shared B cell memory to coronaviruses and other pathogens varies in human age groups and tissues.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.739921164.793585681 ◽

2021 ◽

Author(s):

Mariana Castells

Keyword(s):

B Cell ◽

Age Groups ◽

Cell Memory ◽

B Cell Memory

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Unique Transcriptome Changes in Peripheral B Cells Revealed by Comparing Age Groups From Naive or Vaccinated Mice, Including snoRNA and Cdkn2a

The Journals of Gerontology Series A ◽

10.1093/gerona/glaa165 ◽

2020 ◽

Vol 75 (12) ◽

pp. 2326-2332

Author(s):

Robin L Baudier ◽

Kevin J Zwezdaryk ◽

Malwina Czarny-Ratajczak ◽

Lauren H Kodroff ◽

Deborah E Sullivan ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Middle Age ◽

Age Groups ◽

Principal Component ◽

Cell Cycle Checkpoint ◽

Vaccine Responses ◽

Age Related ◽

Vaccination History ◽

Canonical Pathways

Abstract Aging is associated with a decline in immune function that is not fully understood including vaccine failure. Here we report transcriptomic analysis on B cells from naive or influenza-vaccinated mice of 3 ages: young (15–23 weeks), middle-aged (63–81 weeks), and old mice (103–119 weeks). Our goal was expression profiling of B cells by age and history of vaccination to identify novel changes at the transcriptome level. We observed waning vaccine responses with age. In B cell transcripts, age and vaccination history were both important with notable differences observed in conducted analyses (eg, principal component, gene set enrichment, differentially expressed [DE] genes, and canonical pathways). Only 39 genes were significantly DE with age irrespective of vaccine history. This included age-related changes to box C/D small nucleolar (sno) RNAs, Snord123 and Snord1a. Box C/D snoRNAs regulate rRNAs through methylation and are linked to neurodegenerative, inflammatory, and cancer diseases but not specifically B cells or age. Canonical pathway changes implicated with age irrespective of vaccination history included EIF2, mTOR signaling, p53, Paxillin, and Tec kinase signaling pathways as well as cell cycle checkpoint. Importantly, we identified DE genes and pathways that were progressively altered starting in middle-age (eg, signaling by Rho family GTPases) or only altered in middle-age (eg, sphingosine-1-phosphate signaling), despite minimal differences in the ability of these mice to respond to vaccination compared to younger mice. Our results indicate the importance of vaccination or immune stimulation and analyses of multiple age ranges for aging B cell studies and validate an experimental model for future studies.

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B-Cell Memory Responses to Variant Viral Antigens

Viruses ◽

10.3390/v13040565 ◽

2021 ◽

Vol 13 (4) ◽

pp. 565

Author(s):

Harry N. White

Keyword(s):

Influenza Virus ◽

B Cell ◽

Health Impact ◽

Immune Memory ◽

Central Feature ◽

Cell Memory ◽

B Cell Memory ◽

Shed Light ◽

New Strategies ◽

Virus Influenza

A central feature of vertebrate immune systems is the ability to form antigen-specific immune memory in response to microbial challenge and so provide protection against future infection. In conflict with this process is the ability that many viruses have to mutate their antigens to escape infection- or vaccine-induced antibody memory responses. Mutable viruses such as dengue virus, influenza virus and of course coronavirus have a major global health impact, exacerbated by this ability to evade immune responses through mutation. There have been several outstanding recent studies on B-cell memory that also shed light on the potential and limitations of antibody memory to protect against viral antigen variation, and so promise to inform new strategies for vaccine design. For the purposes of this review, the current understanding of the different memory B-cell (MBC) populations, and their potential to recognize mutant antigens, will be described prior to some examples from antibody responses against the highly mutable RNA based flaviviruses, influenza virus and SARS-CoV-2.

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