Functional and molecular characterization of single, (4-hydroxy-3-nitrophenyl)acetyl (NP)-specific, IgG1+ B cells from antibody-secreting and memory B cell pathways in the C57BL/6 immune response to NP

Abstract Apoptosis is crucial for immune system homeostasis, including selection and survival of long-lived antibody-forming cells and memory cells. The interactions between proapoptotic and pro-survival proteins of the Bcl-2 family are critical for this process. In this report, we show that expression of the proapoptotic BH3-only Bcl-2 family member Puma was selectively up-regulated on in vitro activation with antigens or mitogens of both human and mouse B cells. Puma expression coincided in vivo, with the prosurvival Bcl-2 family member Mcl-1 within the germinal centers and its expression correlates with the germinal center like phenotype of Burkitt lymphoma. Experiments performed in Puma-deficient mice revealed that Puma is essential for apoptosis of mitogen-activated B cells in vitro and for the control of memory B-cell survival. In conclusion, using both human and murine models, our data show that Puma has a major role in the T cell– dependent B-cell immune response. These data demonstrate that Puma is a major regulator of memory B lymphocyte survival and therefore a key molecule in the control of the immune response.

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Characterization of neutralizing versus binding antibodies and memory B cells in COVID-19 recovered individuals from India

10.1101/2020.08.31.276675 ◽

2020 ◽

Author(s):

Kaustuv Nayak ◽

Kamalvishnu Gottimukkala ◽

Sanjeev Kumar ◽

Elluri Seetharami Reddy ◽

Venkata Viswanadh Edara ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Neutralizing Antibody ◽

Memory B Cells ◽

Antibody Responses ◽

Memory B Cell ◽

Specific Memory ◽

Antibody Titers ◽

Specific Igg

AbstractIndia is one of the countries most affected by the recent COVID-19 pandemic. Characterization of humoral responses to SARS-CoV-2 infection, including immunoglobulin isotype usage, neutralizing activity and memory B cell generation, is necessary to provide critical insights on the formation of immune memory in Indian subjects. In this study, we evaluated SARS-CoV-2 receptor-binding domain (RBD)-specific IgG, IgM, and IgA antibody responses, neutralization of live virus, and RBD-specific memory B cell responses in pre-pandemic healthy versus convalescent COVID-19 individuals from India. We observed substantial heterogeneity in the formation of humoral and B cell memory post COVID-19 recovery. While a vast majority (38/42, 90.47%) of COVID-19 recovered individuals developed SARS-CoV-2 RBD-specific IgG responses, only half of them had appreciable neutralizing antibody titers. RBD-specific IgG titers correlated with these neutralizing antibody titers as well as with RBD-specific memory B cell frequencies. In contrast, IgG titers measured against SARS-CoV-2 whole virus preparation, which includes responses to additional viral proteins besides RBD, did not show robust correlation. Our results suggest that assessing RBD-specific IgG titers can serve as a surrogate assay to determine the neutralizing antibody response. These observations have timely implications for identifying potential plasma therapy donors based on RBD-specific IgG in resource-limited settings where routine performance of neutralization assays remains a challenge.ImportanceOur study provides an understanding of SARS-CoV-2-specific neutralizing antibodies, binding antibodies and memory B cells in COVID-19 convalescent subjects from India. Our study highlights that PCR-confirmed convalescent COVID-19 individuals develop SARS-CoV-2 RBD-specific IgG antibodies, which correlate strongly with their neutralizing antibody titers. RBD-specific IgG titers, thus, can serve as a valuable surrogate measurement for neutralizing antibody responses. These finding have timely significance for selection of appropriate individuals as donors for plasma intervention strategies, as well as determining vaccine efficacy.

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Molecular characterization of Treponema pallidum proteins responsible for the human immune response to syphilis

Antonie van Leeuwenhoek ◽

10.1007/bf00448422 ◽

1982 ◽

Vol 48 (5) ◽

pp. 486-487 ◽

Cited By ~ 7

Author(s):

R. V. W. van Eijk ◽

J. D. A. van Embden

Keyword(s):

Immune Response ◽

Molecular Characterization ◽

Treponema Pallidum ◽

Human Immune Response ◽

Human Immune

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Morphologic and Functional Effects of Gamma Secretase Inhibition on Splenic Marginal Zone B Cells

International Journal of Alzheimer s Disease ◽

10.1155/2012/289412 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Maria Cristina de Vera Mudry ◽

Franziska Regenass-Lechner ◽

Laurence Ozmen ◽

Bernd Altmann ◽

Matthias Festag ◽

...

Keyword(s):

Immune Response ◽

B Cells ◽

B Cell ◽

Marginal Zone ◽

Nuclear Translocation ◽

Recovery Period ◽

Functional Characterization ◽

Notch Receptor ◽

Marginal Zone B Cells ◽

Cell Fate Decisions

Theγ-secretase complex is a promising target in Alzheimer’s disease because of its role in the amyloidogenic processing ofβ-amyloid precursor protein. This enzyme also catalyzes the cleavage of Notch receptor, resulting in the nuclear translocation of intracellular Notch where it modulates gene transcription. Notch signaling is essential in cell fate decisions during embryogenesis, neuronal differentiation, hematopoiesis, and development of T and B cells, including splenic marginal zone (MZ) B cells. This B cell compartment participates in the early phases of the immune response to blood-borne bacteria and viruses. Chronic treatment with the oralγ-secretase inhibitor RO4929097 resulted in dose-dependent decreased cellularity (atrophy) of the MZ of rats and mice. Significant decreases in relative MZ B-cell numbers of RO4929097-treated animals were confirmed by flow cytometry. Numbers of MZ B cells reverted to normal after a sufficient RO4929097-free recovery period. Functional characterization of the immune response in relation to RO4929097-related MZ B cell decrease was assessed in mice vaccinated with inactivated vesicular stomatitis virus (VSV). Compared with the immunosuppressant cyclosporin A, RO4929097 caused only mild and reversible delayed early neutralizing IgM and IgG responses to VSV. Thus, the functional consequence of MZ B cell decrease on host defense is comparatively mild.

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Delineation of Human B Cell Differentiation: Immunological and Molecular Characterization of Human B Cell Differentiation Factor (BSF-2)

Mechanisms of Lymphocyte Activation and Immune Regulation - Advances in Experimental Medicine and Biology ◽

10.1007/978-1-4684-5323-2_17 ◽

1987 ◽

pp. 177-188 ◽

Cited By ~ 4

Author(s):

Tadamitsu Kishimoto ◽

Toshio Hirano ◽

Hitoshi Kikutani ◽

Atsushi Muraguchi

Keyword(s):

Cell Differentiation ◽

B Cell ◽

Molecular Characterization ◽

B Cell Differentiation ◽

Differentiation Factor ◽

Cell Differentiation Factor ◽

Human B Cell

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Characterization of human FDCs reveals regulation of T cells and antigen presentation to B cells

Journal of Experimental Medicine ◽

10.1084/jem.20210790 ◽

2021 ◽

Vol 218 (10) ◽

Cited By ~ 1

Author(s):

Balthasar A. Heesters ◽

Kyah van Megesen ◽

Ilhan Tomris ◽

Robert P. de Vries ◽

Giuliana Magri ◽

...

Keyword(s):

T Cells ◽

B Cells ◽

B Cell ◽

Intimate Contact ◽

Expression Of Genes ◽

T Cell Regulation ◽

Native Antigen ◽

Reticular Cells ◽

Molecular Patterns

Stromal-derived follicular dendritic cells (FDCs) are essential for germinal centers (GCs), the site where B cells maturate their antibodies. FDCs present native antigen to B cells and maintain a CXCL13 gradient to form the B cell follicle. Yet despite their essential role, the transcriptome of human FDCs remains undefined. Using single-cell RNA sequencing and microarray, we provided the transcriptome of these enigmatic cells as a comprehensive resource. Key genes were validated by flow cytometry and microscopy. Surprisingly, marginal reticular cells (MRCs) rather than FDCs expressed B cell activating factor (BAFF). Furthermore, we found that human FDCs expressed TLR4 and can alter antigen availability in response to pathogen-associated molecular patterns (PAMPs). High expression of PD-L1 and PD-L2 on FDCs activated PD1 on T cells. In addition, we found expression of genes related to T cell regulation, such as HLA-DRA, CD40, and others. These data suggest intimate contact between human FDCs and T cells.

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Attenuation of Apoptosis Underlies B Lymphocyte Stimulator Enhancement of Humoral Immune Response

Journal of Experimental Medicine ◽

10.1084/jem.192.7.953 ◽

2000 ◽

Vol 192 (7) ◽

pp. 953-964 ◽

Cited By ~ 313

Author(s):

Richard K.G. Do ◽

Eunice Hatada ◽

Hayyoung Lee ◽

Michelle R. Tourigny ◽

David Hilbert ◽

...

Keyword(s):

Immune Response ◽

T Cell ◽

B Cells ◽

B Cell ◽

Cell Survival ◽

B Lymphocyte ◽

Humoral Immune ◽

B Cell Survival ◽

B Lymphocyte Stimulator

B lymphocyte stimulator (BLyS) is a newly identified monocyte-specific TNF family cytokine. It has been implicated in the development of autoimmunity, and functions as a potent costimulator with antiimmunoglobulin M in B cell proliferation in vitro. Here we demonstrate that BLyS prominently enhances the humoral responses to both T cell–independent and T cell–dependent antigens, primarily by attenuation of apoptosis as evidenced by the prolonged survival of antigen-activated B cells in vivo and in vitro. BLyS acts on primary splenic B cells autonomously, and directly cooperates with CD40 ligand (CD40L) in B cell activation in vitro by protecting replicating B cells from apoptosis. Moreover, although BLyS alone cannot activate the cell cycle, it is sufficient to prolong the survival of naive resting B cells in vitro. Attenuation of apoptosis by BLyS correlates with changes in the ratios between Bcl-2 family proteins in favor of cell survival, predominantly by reducing the proapoptotic Bak and increasing its prosurvival partners, Bcl-2 and Bcl-xL. In either resting or CD40L-activated B cells, the NF-κB transcription factors RelB and p50 are specifically activated, suggesting that they may mediate BLyS signals for B cell survival. Together, these results provide direct evidence for BLyS enhancement of both T cell–independent and T cell–dependent humoral immune responses, and imply a role for BLyS in the conservation of the B cell repertoire. The ability of BLyS to increase B cell survival indiscriminately, at either a resting or activated state, and to cooperate with CD40L, further suggests that attenuation of apoptosis underlies BLyS enhancement of polyclonal autoimmunity as well as the physiologic humoral immune response.

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