The Differentiation in vitro of Human Tonsil B Cells With the Phenotypic and Functional Characteristics of T-bet+ Atypical Memory B Cells in Malaria

Malaria is a deadly infectious disease associated with fundamental changes in the composition of the memory B cell (MBC) compartment, most notably a large expansion of T-bet+ MBCs, termed atypical MBCs. However, we know little about the precursors of atypical MBCs and the conditions that drive their...

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Main Authors: Abhijit A. Ambegaonkar, Satoshi Nagata, Susan K. Pierce, Haewon Sohn
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-04-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2019.00852/full
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author Abhijit A. Ambegaonkar
Satoshi Nagata
Susan K. Pierce
Haewon Sohn
author_facet Abhijit A. Ambegaonkar
Satoshi Nagata
Susan K. Pierce
Haewon Sohn
author_sort Abhijit A. Ambegaonkar
collection DOAJ
description Malaria is a deadly infectious disease associated with fundamental changes in the composition of the memory B cell (MBC) compartment, most notably a large expansion of T-bet+ MBCs, termed atypical MBCs. However, we know little about the precursors of atypical MBCs and the conditions that drive their differentiation. We compared the responses of human tonsil naïve B cells, MBCs, and germinal center B cells to a variety of stimulatory conditions. We determined that prolonged antigen presentation in the presence of CpG and IFN-γ induced maximal expression of T-bet and other phenotypic markers of malaria-associated atypical MBCs primarily in naïve B cells in vitro. Importantly T-bet+ naïve-derived B cells resembled atypical MBCs in their hypo-responsiveness to signaling through their B cell receptors. Thus, naïve B cells can be induced to differentiate into phenotypically and functionally atypical-like MBCs in vitro under conditions that may prevail in chronic infectious diseases in vivo.
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spelling doaj.art-5c5cfc39160345f482030c6652c467952022-12-22T00:08:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-04-011010.3389/fimmu.2019.00852434565The Differentiation in vitro of Human Tonsil B Cells With the Phenotypic and Functional Characteristics of T-bet+ Atypical Memory B Cells in MalariaAbhijit A. Ambegaonkar0Satoshi Nagata1Susan K. Pierce2Haewon Sohn3Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, United StatesCenter for Drug Design Research, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, JapanLaboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, United StatesLaboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, United StatesMalaria is a deadly infectious disease associated with fundamental changes in the composition of the memory B cell (MBC) compartment, most notably a large expansion of T-bet+ MBCs, termed atypical MBCs. However, we know little about the precursors of atypical MBCs and the conditions that drive their differentiation. We compared the responses of human tonsil naïve B cells, MBCs, and germinal center B cells to a variety of stimulatory conditions. We determined that prolonged antigen presentation in the presence of CpG and IFN-γ induced maximal expression of T-bet and other phenotypic markers of malaria-associated atypical MBCs primarily in naïve B cells in vitro. Importantly T-bet+ naïve-derived B cells resembled atypical MBCs in their hypo-responsiveness to signaling through their B cell receptors. Thus, naïve B cells can be induced to differentiate into phenotypically and functionally atypical-like MBCs in vitro under conditions that may prevail in chronic infectious diseases in vivo.https://www.frontiersin.org/article/10.3389/fimmu.2019.00852/fullatypical memory B cellsmalariaT-betB cell receptor signalingTLR9IFN-γ
spellingShingle Abhijit A. Ambegaonkar
Satoshi Nagata
Susan K. Pierce
Haewon Sohn
The Differentiation in vitro of Human Tonsil B Cells With the Phenotypic and Functional Characteristics of T-bet+ Atypical Memory B Cells in Malaria
Frontiers in Immunology
atypical memory B cells
malaria
T-bet
B cell receptor signaling
TLR9
IFN-γ
title The Differentiation in vitro of Human Tonsil B Cells With the Phenotypic and Functional Characteristics of T-bet+ Atypical Memory B Cells in Malaria
title_full The Differentiation in vitro of Human Tonsil B Cells With the Phenotypic and Functional Characteristics of T-bet+ Atypical Memory B Cells in Malaria
title_fullStr The Differentiation in vitro of Human Tonsil B Cells With the Phenotypic and Functional Characteristics of T-bet+ Atypical Memory B Cells in Malaria
title_full_unstemmed The Differentiation in vitro of Human Tonsil B Cells With the Phenotypic and Functional Characteristics of T-bet+ Atypical Memory B Cells in Malaria
title_short The Differentiation in vitro of Human Tonsil B Cells With the Phenotypic and Functional Characteristics of T-bet+ Atypical Memory B Cells in Malaria
title_sort differentiation in vitro of human tonsil b cells with the phenotypic and functional characteristics of t bet atypical memory b cells in malaria
topic atypical memory B cells
malaria
T-bet
B cell receptor signaling
TLR9
IFN-γ
url https://www.frontiersin.org/article/10.3389/fimmu.2019.00852/full
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