B-Cell Response during Protozoan Parasite Infections

In this review, we discuss how protozoan parasites alter immature and mature B cell compartment. B1 and marginal zone (MZ) B cells, considered innate like B cells, are activated during protozoan parasite infections, and they generate short lived plasma cells providing a prompt antibody source. In addition, protozoan infections induce massive B cell response with polyclonal activation that leads to hypergammaglobulnemia with serum antibodies specific for the parasites and self and/or non related antigens. To protect themselves, the parasites have evolved unique ways to evade B cell immune responses inducing apoptosis of MZ and conventional mature B cells. As a consequence of the parasite induced-apoptosis, the early IgM response and an already establish humoral immunity are affected during the protozoan parasite infection. Moreover, some trypanosomatides trigger bone marrow immature B cell apoptosis, influencing the generation of new mature B cells. Simultaneously with their ability to release antibodies, B cells produce cytokines/quemokines that influence the characteristic of cellular immune response and consequently the progression of parasite infections.

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SARS-CoV-2 specific memory B cells frequency in recovered patient remains stable while antibodies decay over time

10.1101/2020.08.23.20179796 ◽

2020 ◽

Cited By ~ 2

Author(s):

Anna Vaisman-Mentesh ◽

Yael Dror ◽

Ran Tur-Kaspa ◽

Dana Markovitch ◽

Tatiana Kournos ◽

...

Keyword(s):

B Cells ◽

Antibody Response ◽

B Cell ◽

Cell Response ◽

Plasma Cells ◽

Memory B Cells ◽

Humoral Immune ◽

Specific Memory ◽

Over Time ◽

B Cell Response

The breadth of the humoral immune response following SARS-CoV-2 infection was indicated to be important for recovery from COVID-19. Recent studies have provided valuable insights regarding the dynamics of the antibody response in symptomatic COVID-19 patients. However, the information regarding the dynamics of the serological and cellular memory in COVID-19 recovered patients in scarce. It is imperative to determine the persistence of humoral memory in COVID-19 recovered patients as it will help to evaluate the susceptibility of recovered patients to re-infection. Here, we describe the dynamics of both the SARS-CoV-2 specific serological and B cell response in COVID-19 recovered patients. We found that symptomatic SARS-CoV-2 patients mount a robust antibody response following infection however, the serological memory decays in recovered patients over the period of 6 months. On the other hand, the B cell response as observed in the SARS-CoV-2 specific memory B cell compartment, was found to be stable over time. Moreover, the frequency of SARS-CoV-2 specific B cell plasmablasts was found to be associated with the SARS-CoV-2 specific antibody levels. These data, suggests that the differentiation of short-lived plasmablasts to become long-lived plasma cells is impaired and the main contributor of antibody production are the short-lived plasmablasts. Overall, our data provides insights regarding the humoral memory persistence in recovered COVID-19 patients. Notwithstanding the insights from this study, it is still to be determined if the persistence of SARS-CoV-2 memory B cells can be considered as a correlate of protection in the absence of serological memory.

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Lethal Coinfection of Influenza Virus and Streptococcus pneumoniae Lowers Antibody Response to Influenza Virus in Lung and Reduces Numbers of Germinal Center B Cells, T Follicular Helper Cells, and Plasma Cells in Mediastinal Lymph Node

Journal of Virology ◽

10.1128/jvi.02455-14 ◽

2014 ◽

Vol 89 (4) ◽

pp. 2013-2023 ◽

Cited By ~ 11

Author(s):

Yuet Wu ◽

Wenwei Tu ◽

Kwok-Tai Lam ◽

Kin-Hung Chow ◽

Pak-Leung Ho ◽

...

Keyword(s):

Influenza Virus ◽

B Cells ◽

Virus Infection ◽

B Cell ◽

Cell Response ◽

Plasma Cells ◽

Pneumococcal Infection ◽

Influenza Virus Infection ◽

Follicular Helper ◽

B Cell Response

ABSTRACTSecondaryStreptococcus pneumoniaeinfection after influenza is a significant clinical complication resulting in morbidity and sometimes mortality. Prior influenza virus infection has been demonstrated to impair the macrophage and neutrophil response to the subsequent pneumococcal infection. In contrast, how a secondary pneumococcal infection after influenza can affect the adaptive immune response to the initial influenza virus infection is less well understood. Therefore, this study focuses on how secondary pneumococcal infection after influenza may impact the humoral immune response to the initial influenza virus infection in a lethal coinfection mouse model. Compared to mice infected with influenza virus alone, mice coinfected with influenza virus followed by pneumococcus had significant body weight loss and 100% mortality. In the lung, lethal coinfection significantly increased virus titers and bacterial cell counts and decreased the level of virus-specific IgG, IgM, and IgA, as well as the number of B cells, CD4 T cells, and plasma cells. Lethal coinfection significantly reduced the size and weight of spleen, as well as the number of B cells along the follicular developmental lineage. In mediastinal lymph nodes, lethal coinfection significantly decreased germinal center B cells, T follicular helper cells, and plasma cells. Adoptive transfer of influenza virus-specific immune serum to coinfected mice improved survival, suggesting the protective functions of anti-influenza virus antibodies. In conclusion, coinfection reduced the B cell response to influenza virus. This study helps us to understand the modulation of the B cell response to influenza virus during a lethal coinfection.IMPORTANCESecondary pneumococcal infection after influenza virus infection is an important clinical issue that often results in excess mortality. Since antibodies are key mediators of protection, this study aims to examine the antibody response to influenza virus and demonstrates that lethal coinfection reduced the B cell response to influenza virus. This study helps to highlight the complexity of the modulation of the B cell response in the context of coinfection.

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Appearance of peripheral blood plasma cells and memory B cells in a primary and secondary immune response in humans

Blood ◽

10.1182/blood-2009-03-211052 ◽

2009 ◽

Vol 114 (24) ◽

pp. 4998-5002 ◽

Cited By ~ 67

Author(s):

Geraldine Blanchard-Rohner ◽

Anoop S. Pulickal ◽

Cornelia M. Jol-van der Zijde ◽

Matthew D. Snape ◽

Andrew J. Pollard

Keyword(s):

B Cells ◽

B Cell ◽

Cell Response ◽

Plasma Cells ◽

Rabies Vaccine ◽

Memory B Cells ◽

Naive Group ◽

Peripheral Blood Plasma ◽

Kinetics Of ◽

B Cell Response

AbstractIn humans, the kinetics of the appearance of memory B cells and plasma cells during primary immunization are not well defined. In this study, we assessed the primary B-cell response of rabies-antigen naive volunteers during a 3-dose course of rabies vaccine compared with the B-cell response to a booster dose of rabies vaccine given to previously immunized volunteers. After a single dose of vaccine, in the naive group plasma and memory B cells appeared later (peak at day 10) than in the primed group (peak at day 7) and were at lower frequency. The most rapid responses (day 4) were detected after a third immunization in the naive group. This is the first study to document the detailed kinetics of the plasma cell and memory B-cell responses to immunization in adult humans and to demonstrate differences in the responses that relate to the preexisting immune status of the persons.

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Hemolysis Inhibits Humoral B Cell Responses and Modulates Alloimmunization Risk in Patients with Sickle Cell Disease

Blood ◽

10.1182/blood.2020008511 ◽

2020 ◽

Author(s):

Mouli Pal ◽

Weili Bao ◽

Rikang Wang ◽

Yunfeng Liu ◽

Xiuli An ◽

...

Keyword(s):

B Cells ◽

Sickle Cell Disease ◽

B Cell ◽

Sickle Cell ◽

Cell Response ◽

Cell Activity ◽

Immunomodulatory Activity ◽

Heme Oxygenase 1 ◽

Cell Disease ◽

B Cell Response

Red blood cell alloimmunization remains a barrier for safe and effective transfusions in sickle cell disease (SCD), but the associated risk factors remain largely unknown. Intravascular hemolysis, a hallmark of SCD, results in the release of heme with potent immunomodulatory activity, although its effect on SCD humoral response, specifically alloimmunization, remains unclear. Here, we found that cell-free heme suppresses human B cell plasmablast/plasma cell differentiation by inhibiting the DOCK8/STAT3 signaling pathway, which is critical for B cell activation, as well as by upregulating heme oxygenase 1 (HO-1) through its enzymatic byproducts, carbon monoxide and biliverdin. Whereas non-alloimmunized SCD B cells were inhibited by exogenous heme, B cells from the alloimmunized group were non-responsive to heme inhibition and readily differentiated into plasma cells. Consistent with a differential B cell response to hemolysis, we found elevated B cell basal levels of DOCK8 and higher HO-1-mediated inhibition of activated B cells in non-alloimmunized compared to alloimmunized SCD patients. To overcome the alloimmunized B cell heme insensitivity, we screened several heme-binding molecules and identified quinine as a potent inhibitor of B cell activity, reversing the resistance to heme suppression in alloimmunized patients. B cell inhibition by quinine only occurred in the presence of heme and through HO-1 induction. Altogether, these data suggest that hemolysis can dampen the humoral B cell response and that B cell heme responsiveness maybe a determinant of alloimmunization risk in SCD. Quinine by restoring B cell heme sensitivity may have therapeutic potential to prevent and inhibit alloimmunization in SCD patients.

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Biomaterials direct functional B cell response in a material specific manner

10.1101/2021.01.12.426347 ◽

2021 ◽

Author(s):

Erika M. Moore ◽

David R. Maestas ◽

Chris C. Cherry ◽

Jordan A. Garcia ◽

Hannah Y. Comeau ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Cell Response ◽

Tissue Injury ◽

Breast Implants ◽

Cell Immune Response ◽

Biomaterial Scaffold ◽

Scaffold Materials ◽

Antigen Presenting ◽

B Cell Response

AbstractB cells are an adaptive immune target of biomaterials development in vaccine research but despite their role in wound healing have not been studied in tissue engineering and regenerative medicine. We evaluated the B cell response to biomaterial scaffold materials implanted in a muscle wound; a biological extracellular matrix (ECM) and synthetic polyester polycaprolactone. In the local muscle tissue, small numbers of B cells are recruited in response to tissue injury and biomaterial implantation. ECM materials induced plasmablasts in lymph nodes and antigen presentation in the spleen while the synthetic PCL implants delayed B cell migration and induced an antigen presenting phenotype. In muMt− mice lacking B cells, the fibrotic response to the synthetic biomaterials decreased. Immunofluorescence confirmed antigen presenting B cells in fibrotic tissue surrounding silicone breast implants. In sum, the adaptive B cell immune response to biomaterial depends on composition and induces local, regional and systemic immunological changes.

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SARS-CoV-2 spike-specific memory B cells express higher levels of T-bet and FcRL5 after non-severe COVID-19 as compared to severe disease

PLoS ONE ◽

10.1371/journal.pone.0261656 ◽

2021 ◽

Vol 16 (12) ◽

pp. e0261656

Author(s):

Raphael A. Reyes ◽

Kathleen Clarke ◽

S. Jake Gonzales ◽

Angelene M. Cantwell ◽

Rolando Garza ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Symptom Onset ◽

Cell Response ◽

Severe Disease ◽

Memory B Cells ◽

Memory B Cell ◽

Specific Memory ◽

Specific Igg ◽

B Cell Response

SARS-CoV-2 infection elicits a robust B cell response, resulting in the generation of long-lived plasma cells and memory B cells. Here, we aimed to determine the effect of COVID-19 severity on the memory B cell response and characterize changes in the memory B cell compartment between recovery and five months post-symptom onset. Using high-parameter spectral flow cytometry, we analyzed the phenotype of memory B cells with reactivity against the SARS-CoV-2 spike protein or the spike receptor binding domain (RBD) in recovered individuals who had been hospitalized with non-severe (n = 8) or severe (n = 5) COVID-19. One month after symptom onset, a substantial proportion of spike-specific IgG+ B cells showed an activated phenotype. In individuals who experienced non-severe disease, spike-specific IgG+ B cells showed increased expression of markers associated with durable B cell memory, including T-bet and FcRL5, as compared to individuals who experienced severe disease. While the frequency of T-bet+ spike-specific IgG+ B cells differed between the two groups, these cells predominantly showed an activated switched memory B cell phenotype in both groups. Five months post-symptom onset, the majority of spike-specific memory B cells had a resting phenotype and the percentage of spike-specific T-bet+ IgG+ memory B cells decreased to baseline levels. Collectively, our results highlight subtle differences in the B cells response after non-severe and severe COVID-19 and suggest that the memory B cell response elicited during non-severe COVID-19 may be of higher quality than the response after severe disease.

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Germ line tumor-associated immunoglobulin VH region peptides provoke a tumor-specific immune response without altering the response potential of normal B cells

Blood ◽

10.1182/blood-2004-01-0105 ◽

2004 ◽

Vol 104 (3) ◽

pp. 752-759 ◽

Cited By ~ 9

Author(s):

Qiang Lou ◽

Raymond J. Kelleher ◽

Alessandro Sette ◽

Jenni Loyall ◽

Scott Southwood ◽

...

Keyword(s):

Immune Response ◽

B Cells ◽

B Cell ◽

Cell Response ◽

Germ Line ◽

T Cell Response ◽

Binding Potential ◽

Variable Regions ◽

B Cell Response

AbstractPrevious studies have suggested that murine T cells are tolerant to epitopes derived from germ line variable regions of immunoglobulin (Ig) heavy (VH) or light chains. This has lead to the prediction that germ line VH-region epitopes found in neoplastic B cells cannot be used to provoke an antitumor immune response. To test these assumptions and address the question of how such a vaccine may alter the normal B-cell response, an antibody-forming B-cell hybridoma (1H6) expressing a conserved germ line VH gene with specificity for dextran was generated and used as a tumor model. Using algorithms for predicting major histocompatibility complex (MHC) binding, potential MHC class I and II binding peptides were identified within the 1H6 VH region, synthesized, and tested for MHC binding and immunogenicity. We show that germ line VH peptides, when presented by dendritic cells, are immunogenic in vitro and provoke a tumor-specific protective immune response in vivo. We conclude that (1) it is possible to induce a T-cell response to germ line VH peptides; (2) such peptides can be used to generate a B-cell tumor-specific vaccine; and (3) a vaccine targeting VH peptides expressed by the dominant dextran-specific B-cell clonotype had no effect upon the magnitude of the normal B-cell response to dextran.

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High Preexisting Serological Antibody Levels Correlate with Diversification of the Influenza Vaccine Response

Journal of Virology ◽

10.1128/jvi.02871-14 ◽

2015 ◽

Vol 89 (6) ◽

pp. 3308-3317 ◽

Cited By ~ 74

Author(s):

Sarah F. Andrews ◽

Kaval Kaur ◽

Noel T. Pauli ◽

Min Huang ◽

Yunping Huang ◽

...

Keyword(s):

Influenza Virus ◽

B Cells ◽

Influenza Vaccine ◽

B Cell ◽

Cell Response ◽

Vaccine Response ◽

Trivalent Influenza Vaccine ◽

Antibody Levels ◽

Virus Strains ◽

B Cell Response

ABSTRACTReactivation of memory B cells allows for a rapid and robust immune response upon challenge with the same antigen. Variant influenza virus strains generated through antigenic shift or drift are encountered multiple times over the lifetime of an individual. One might predict, then, that upon vaccination with the trivalent influenza vaccine across multiple years, the antibody response would become more and more dominant toward strains consistently present in the vaccine at the expense of more divergent strains. However, when we analyzed the vaccine-induced plasmablast, memory, and serological responses to the trivalent influenza vaccine between 2006 and 2013, we found that the B cell response was most robust against more divergent strains. Overall, the antibody response was highest when one or more strains contained in the vaccine varied from year to year. This suggests that in the broader immunological context of viral antigen exposure, the B cell response to variant influenza virus strains is not dictated by the composition of the memory B cell precursor pool. The outcome is instead a diversified B cell response.IMPORTANCEVaccine strategies are being designed to boost broadly reactive B cells present in the memory repertoire to provide universal protection to the influenza virus. It is important to understand how past exposure to influenza virus strains affects the response to subsequent immunizations. The viral epitopes targeted by B cells responding to the vaccine may be a direct reflection of the B cell memory specificities abundant in the preexisting immune repertoire, or other factors may influence the vaccine response. Here, we demonstrate that high preexisting serological antibody levels to a given influenza virus strain correlate with low production of antibody-secreting cells and memory B cells recognizing that strain upon revaccination. In contrast, introduction of antigenically novel strains generates a robust B cell response. Thus, both the preexisting memory B cell repertoire and serological antibody levels must be taken into consideration in predicting the quality of the B cell response to new prime-boost vaccine strategies.

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Light chain skewing in autoantibodies and B-cell receptors of the citrullinated antigen-binding B-cell response in rheumatoid arthritis

PLoS ONE ◽

10.1371/journal.pone.0247847 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0247847

Author(s):

Linda M. Slot ◽

Rochelle D. Vergroesen ◽

Priscilla F. Kerkman ◽

Ellen Staudinger ◽

Sanne Reijm ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

B Cells ◽

B Cell ◽

Light Chain ◽

Cell Response ◽

World Population ◽

Antigen Binding ◽

Cell Repertoire ◽

Citrullinated Antigen ◽

B Cell Response

Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting 1% of the world population. RA is associated with the presence of autoantibodies, of which anti-citrullinated protein antibodies (ACPA) are most prominent. ACPA are produced by citrullinated antigen-binding B cells that have presumably survived tolerance checkpoints. So far, it is unclear how and when such autoreactive B cells emerge. Light chain (LC) rearrangement and mutation rates can be informative with regard to selection steps during B-cell development. Therefore, we studied LC characteristics of ACPA-expressing B cells and secreted ACPA with the aim to better understand the development of this disease-specific, autoreactive B-cell response. Paired ACPA-IgG and ACPA-depleted IgG were isolated from serum (n = 87) and synovial fluid (SF, n = 21) of patients with established RA. We determined the LC composition for each fraction by ELISA using kappa(Igκ)- and lambda(Igλ) LC-specific antibodies. Cellular LC expression was determined using flow cytometry. In addition, we used a B-cell receptor (BCR)-specific PCR to obtain LC variable region sequences of citrullinated antigen- and tetanus toxoid (TT)-binding B cells. In serum, we observed an increased frequency of lambda LC in ACPA-IgG (1.64:1) compared to control IgG (2.03:1) and to the κ/λ ratio reported for healthy individuals (2:1). A similar trend towards higher frequencies of lambda LCs was observed for ACPA-IgG in SF (1.84:1). Additionally, the percentage of Igλ-expressing B cells was higher for citrullinated antigen-binding B cells (51%) compared to TT-specific (43%) and total CD19+CD20+ B cells (36%). Moreover, an increased Igλ percentage was observed in BCR-sequences derived from ACPA-expressing (49%) compared to TT-specific B cells (34%). Taken together, we report an enhanced frequency of lambda LCs in the secreted ACPA-IgG repertoire and, on the cellular level, in BCR sequences of ACPA-expressing B cells compared to control. This skewing in the autoreactive B-cell repertoire could reflect a process of active selection.

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P092 Pathogenic B-cell response in ulcerative colitis that associates with treatment resistance and disease complications

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.221 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S181-S182

Author(s):

M Uzzan ◽

J Martin ◽

E Keningsberg ◽

T Castro-Dopico ◽

R Huang ◽

...

Keyword(s):

Ulcerative Colitis ◽

B Cells ◽

B Cell ◽

Healthy Volunteers ◽

Single Cell ◽

Cell Response ◽

Validation Cohort ◽

Multiparameter Flow Cytometry ◽

Adaptive Immune Cells ◽

B Cell Response

Abstract Background Among the adaptive immune cells, B cells, dominated by IgA producing plasma cells (PC), are critical for intestinal homeostasis. However, the B-cell response remains under studied in ulcerative colitis (UC). Methods Using single-cell RNA sequencing (scRNA seq), single-cell IgH sequencing (sc IgH seq), multiparameter flow cytometry (FC), mass cytometry (MC) and immunofluorescent microscopy (IF), we have comprehensively defined the landscape of intestinal and circulating B cells in patients with UC. A Cohort of 88 patients with active UC, 14 patients with quiescent UC and 43 healthy volunteers were recruited. Two validation cohorts comprising of 53 patients with active UC, 59 patients with quiescent UC and 65 healthy volunteers (Validation cohort 1) and 65 patients with active UC, 42 patients with quiescent UC and 36 healthy volunteers (Validation cohort 2) were also studied. Results scRNA seq and FC demonstrate a dramatic increase in proliferating (Ki67+) plasmablasts (PB) as well as IgG+ PC in the inflamed colon of UC patients. Additionally, a significant increase in short-lived (CD19+CD45+) PC was observed during colonic inflammation. scIgH seq further demonstrates a significant decrease in somatic hypermutations and the diversity of intestinal PC of patients with active UC. Genes associated with Fc-dependent macrophage signalling were enriched in areas of active disease and were associated with non-response to TNF therapy. In circulation, a significant increase in a4b7+ gut-homing PC was noted that related to disease extent, severity and complications (defined by treatment non-response, hospitalisations and surgery). Conclusion Active UC results in an immature, IgG-dominated PB/PC response in inflamed GI tissue and an increase in the frequency of gut-homing PC in circulation that relates to disease activity and complications and may be used to monitor disease course. These data provide novel insights into the pathogenesis of UC with major implications for existing and emerging therapeutic agents.

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