Liver Is a Generative Site for the B Cell Response to Ehrlichia muris

Nikita Trivedi; Florian Weisel; Shuchi Smita; Stephen Joachim; Muhamuda Kader; Aditya Radhakrishnan; Chris Clouser; Aaron M. Rosenfeld; Maria Chikina; Francois Vigneault; Uri Hershberg; Nahed Ismail; Mark Jay Shlomchik

doi:10.1016/j.immuni.2019.10.004

Liver Is a Generative Site for the B Cell Response to Ehrlichia muris

Nikita Trivedi, Florian Weisel, Shuchi Smita, Stephen Joachim, Muhamuda Kader, Aditya Radhakrishnan, Chris Clouser, Aaron M. Rosenfeld, Maria Chikina, Francois Vigneault, Uri Hershberg, Nahed Ismail, Mark Jay Shlomchik

Research output: Contribution to journal › Article › peer-review

Abstract

The B cell response to Ehrlichia muris is dominated by plasmablasts (PBs), with few—if any—germinal centers (GCs), yet it generates protective immunoglobulin M (IgM) memory B cells (MBCs) that express the transcription factor T-bet and harbor V-region mutations. Because Ehrlichia prominently infects the liver, we investigated the nature of liver B cell response and that of the spleen. B cells within infected livers proliferated and underwent somatic hypermutation (SHM). Vh-region sequencing revealed trafficking of clones between the spleen and liver and often subsequent local clonal expansion and intraparenchymal localization of T-bet⁺ MBCs. T-bet⁺ MBCs expressed MBC subset markers CD80 and PD-L2. Many T-bet⁺ MBCs lacked CD11b or CD11c expression but had marginal zone (MZ) B cell phenotypes and colonized the splenic MZ, revealing T-bet⁺ MBC plasticity. Hence, liver and spleen are generative sites of B cell responses, and they include V-region mutation and result in liver MBC localization.

Original language	English
Pages (from-to)	1088-1101.e5
Journal	Immunity
Volume	51
Issue number	6
DOIs	https://doi.org/10.1016/j.immuni.2019.10.004
State	Published - 17 Dec 2019
Externally published	Yes

Bibliographical note

Funding Information:
We thank Dr. David Walker at the University of Texas Medical Branch for providing E. muris Ags Omp12 and Omp19. We thank the Histology Core at Magee Research Institute for laser micro-dissections. We are thankful to Laura Conter and Rachel Green for helping with the experiments. This work was funded by NIH grants NIH-1R01AI105018 and NIH-2R01AI043603 . A.M.R. was supported by NIH grant P01-AI106697 .

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

Ehrlichia muris
T-bet
age-associated B cells
liver
memory B cells
plasmablasts
somatic hypermutation

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.immuni.2019.10.004

Cite this

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title = "Liver Is a Generative Site for the B Cell Response to Ehrlichia muris",

abstract = "The B cell response to Ehrlichia muris is dominated by plasmablasts (PBs), with few—if any—germinal centers (GCs), yet it generates protective immunoglobulin M (IgM) memory B cells (MBCs) that express the transcription factor T-bet and harbor V-region mutations. Because Ehrlichia prominently infects the liver, we investigated the nature of liver B cell response and that of the spleen. B cells within infected livers proliferated and underwent somatic hypermutation (SHM). Vh-region sequencing revealed trafficking of clones between the spleen and liver and often subsequent local clonal expansion and intraparenchymal localization of T-bet+ MBCs. T-bet+ MBCs expressed MBC subset markers CD80 and PD-L2. Many T-bet+ MBCs lacked CD11b or CD11c expression but had marginal zone (MZ) B cell phenotypes and colonized the splenic MZ, revealing T-bet+ MBC plasticity. Hence, liver and spleen are generative sites of B cell responses, and they include V-region mutation and result in liver MBC localization.",

keywords = "Ehrlichia muris, T-bet, age-associated B cells, liver, memory B cells, plasmablasts, somatic hypermutation",

author = "Nikita Trivedi and Florian Weisel and Shuchi Smita and Stephen Joachim and Muhamuda Kader and Aditya Radhakrishnan and Chris Clouser and Rosenfeld, {Aaron M.} and Maria Chikina and Francois Vigneault and Uri Hershberg and Nahed Ismail and Shlomchik, {Mark Jay}",

note = "Funding Information: We thank Dr. David Walker at the University of Texas Medical Branch for providing E. muris Ags Omp12 and Omp19. We thank the Histology Core at Magee Research Institute for laser micro-dissections. We are thankful to Laura Conter and Rachel Green for helping with the experiments. This work was funded by NIH grants NIH-1R01AI105018 and NIH-2R01AI043603 . A.M.R. was supported by NIH grant P01-AI106697 . Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

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AU - Trivedi, Nikita

AU - Weisel, Florian

AU - Smita, Shuchi

AU - Joachim, Stephen

AU - Kader, Muhamuda

AU - Radhakrishnan, Aditya

AU - Clouser, Chris

AU - Rosenfeld, Aaron M.

AU - Chikina, Maria

AU - Vigneault, Francois

AU - Hershberg, Uri

AU - Ismail, Nahed

AU - Shlomchik, Mark Jay

N1 - Funding Information: We thank Dr. David Walker at the University of Texas Medical Branch for providing E. muris Ags Omp12 and Omp19. We thank the Histology Core at Magee Research Institute for laser micro-dissections. We are thankful to Laura Conter and Rachel Green for helping with the experiments. This work was funded by NIH grants NIH-1R01AI105018 and NIH-2R01AI043603 . A.M.R. was supported by NIH grant P01-AI106697 . Publisher Copyright: © 2019 Elsevier Inc.

PY - 2019/12/17

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N2 - The B cell response to Ehrlichia muris is dominated by plasmablasts (PBs), with few—if any—germinal centers (GCs), yet it generates protective immunoglobulin M (IgM) memory B cells (MBCs) that express the transcription factor T-bet and harbor V-region mutations. Because Ehrlichia prominently infects the liver, we investigated the nature of liver B cell response and that of the spleen. B cells within infected livers proliferated and underwent somatic hypermutation (SHM). Vh-region sequencing revealed trafficking of clones between the spleen and liver and often subsequent local clonal expansion and intraparenchymal localization of T-bet+ MBCs. T-bet+ MBCs expressed MBC subset markers CD80 and PD-L2. Many T-bet+ MBCs lacked CD11b or CD11c expression but had marginal zone (MZ) B cell phenotypes and colonized the splenic MZ, revealing T-bet+ MBC plasticity. Hence, liver and spleen are generative sites of B cell responses, and they include V-region mutation and result in liver MBC localization.

AB - The B cell response to Ehrlichia muris is dominated by plasmablasts (PBs), with few—if any—germinal centers (GCs), yet it generates protective immunoglobulin M (IgM) memory B cells (MBCs) that express the transcription factor T-bet and harbor V-region mutations. Because Ehrlichia prominently infects the liver, we investigated the nature of liver B cell response and that of the spleen. B cells within infected livers proliferated and underwent somatic hypermutation (SHM). Vh-region sequencing revealed trafficking of clones between the spleen and liver and often subsequent local clonal expansion and intraparenchymal localization of T-bet+ MBCs. T-bet+ MBCs expressed MBC subset markers CD80 and PD-L2. Many T-bet+ MBCs lacked CD11b or CD11c expression but had marginal zone (MZ) B cell phenotypes and colonized the splenic MZ, revealing T-bet+ MBC plasticity. Hence, liver and spleen are generative sites of B cell responses, and they include V-region mutation and result in liver MBC localization.

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JF - Immunity

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ER -

Liver Is a Generative Site for the B Cell Response to Ehrlichia muris

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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