α4-integrin deficiency in B cells does not affect disease in a T-cell-mediated EAE disease model

Research output: Contribution to journalArticle

Rehana Z. Hussain, Petra D. Cravens, William A. Miller-Little, Richard Doelger, Valerie Granados, Emily Herndon, Darin T. Okuda, Todd N. Eagar, Olaf Stüve

ObjectiveThe goal of this study was to investigate the role of CD 19+ B cells within the brain and spinal cord during CNS autoimmunity in a peptide-induced, primarily T-cell-mediated experimental autoimmune encephalomyelitis (EAE) model of MS. We hypothesized that CD19+ B cells outside the CNS drive inflammation in EAE.MethodsWe generated CD19.Cre+/- α4-integrinfl/fl mice. EAE was induced by active immunization with myelin oligodendrocyte glycoprotein peptide (MOGp35-55). Multiparameter flow cytometry was used to phenotype leukocyte subsets in primary and secondary lymphoid organs and the CNS. Serum cytokine levels and Ig levels were assessed by bead array. B-cell adoptive transfer was used to determine the compartment-specific pathogenic role of antigen-specific and non-antigen-specific B cells.ResultsA genetic ablation of α4-integrin in CD19+/- B cells significantly reduced the number of CD19+ B cells in the CNS but does not affect EAE disease activity in active MOGp35-55-induced disease. The composition of B-cell subsets in the brain, primary lymphoid organs, and secondary lymphoid organs of CD19.Cre+/- α4-integrinfl/fl mice was unchanged during MOGp35-55-induced EAE. Adoptive transfer of purified CD19+ B cells from CD19.Cre+/- α4-integrinfl/fl mice or C57BL/6 wild-type (WT) control mice immunized with recombinant rMOG1-125 or ovalbumin323-339 into MOGp35-55-immunized CD19.Cre+/- α4-integrinfl/fl mice caused worse clinical EAE than was observed in MOGp35-55-immunized C57BL/6 WT control mice that did not receive adoptively transferred CD19+ B cells.ConclusionsObservations made in CD19.Cre+/- α4-integrinfl/fl mice in active MOGp35-55-induced EAE suggest a compartment-specific pathogenic role of CD19+ B cells mostly outside of the CNS that is not necessarily antigen specific.

Original languageEnglish (US)
Article numbere563
JournalNeurology: Neuroimmunology and NeuroInflammation
Volume6
Issue number4
DOIs
StatePublished - Jul 1 2019

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α4-integrin deficiency in B cells does not affect disease in a T-cell-mediated EAE disease model. / Hussain, Rehana Z.; Cravens, Petra D.; Miller-Little, William A.; Doelger, Richard; Granados, Valerie; Herndon, Emily; Okuda, Darin T.; Eagar, Todd N.; Stüve, Olaf.

In: Neurology: Neuroimmunology and NeuroInflammation, Vol. 6, No. 4, e563, 01.07.2019.

Research output: Contribution to journalArticle

Harvard

Hussain, RZ, Cravens, PD, Miller-Little, WA, Doelger, R, Granados, V, Herndon, E, Okuda, DT, Eagar, TN & Stüve, O 2019, 'α4-integrin deficiency in B cells does not affect disease in a T-cell-mediated EAE disease model' Neurology: Neuroimmunology and NeuroInflammation, vol. 6, no. 4, e563. https://doi.org/10.1212/NXI.0000000000000563

APA

Hussain, R. Z., Cravens, P. D., Miller-Little, W. A., Doelger, R., Granados, V., Herndon, E., ... Stüve, O. (2019). α4-integrin deficiency in B cells does not affect disease in a T-cell-mediated EAE disease model. Neurology: Neuroimmunology and NeuroInflammation, 6(4), [e563]. https://doi.org/10.1212/NXI.0000000000000563

Vancouver

Hussain RZ, Cravens PD, Miller-Little WA, Doelger R, Granados V, Herndon E et al. α4-integrin deficiency in B cells does not affect disease in a T-cell-mediated EAE disease model. Neurology: Neuroimmunology and NeuroInflammation. 2019 Jul 1;6(4). e563. https://doi.org/10.1212/NXI.0000000000000563

Author

Hussain, Rehana Z. ; Cravens, Petra D. ; Miller-Little, William A. ; Doelger, Richard ; Granados, Valerie ; Herndon, Emily ; Okuda, Darin T. ; Eagar, Todd N. ; Stüve, Olaf. / α4-integrin deficiency in B cells does not affect disease in a T-cell-mediated EAE disease model. In: Neurology: Neuroimmunology and NeuroInflammation. 2019 ; Vol. 6, No. 4.

BibTeX

@article{a5e61b573abb4ab489839f46a9a87b06,
title = "α4-integrin deficiency in B cells does not affect disease in a T-cell-mediated EAE disease model",
abstract = "ObjectiveThe goal of this study was to investigate the role of CD 19+ B cells within the brain and spinal cord during CNS autoimmunity in a peptide-induced, primarily T-cell-mediated experimental autoimmune encephalomyelitis (EAE) model of MS. We hypothesized that CD19+ B cells outside the CNS drive inflammation in EAE.MethodsWe generated CD19.Cre+/- α4-integrinfl/fl mice. EAE was induced by active immunization with myelin oligodendrocyte glycoprotein peptide (MOGp35-55). Multiparameter flow cytometry was used to phenotype leukocyte subsets in primary and secondary lymphoid organs and the CNS. Serum cytokine levels and Ig levels were assessed by bead array. B-cell adoptive transfer was used to determine the compartment-specific pathogenic role of antigen-specific and non-antigen-specific B cells.ResultsA genetic ablation of α4-integrin in CD19+/- B cells significantly reduced the number of CD19+ B cells in the CNS but does not affect EAE disease activity in active MOGp35-55-induced disease. The composition of B-cell subsets in the brain, primary lymphoid organs, and secondary lymphoid organs of CD19.Cre+/- α4-integrinfl/fl mice was unchanged during MOGp35-55-induced EAE. Adoptive transfer of purified CD19+ B cells from CD19.Cre+/- α4-integrinfl/fl mice or C57BL/6 wild-type (WT) control mice immunized with recombinant rMOG1-125 or ovalbumin323-339 into MOGp35-55-immunized CD19.Cre+/- α4-integrinfl/fl mice caused worse clinical EAE than was observed in MOGp35-55-immunized C57BL/6 WT control mice that did not receive adoptively transferred CD19+ B cells.ConclusionsObservations made in CD19.Cre+/- α4-integrinfl/fl mice in active MOGp35-55-induced EAE suggest a compartment-specific pathogenic role of CD19+ B cells mostly outside of the CNS that is not necessarily antigen specific.",
author = "Hussain, {Rehana Z.} and Cravens, {Petra D.} and Miller-Little, {William A.} and Richard Doelger and Valerie Granados and Emily Herndon and Okuda, {Darin T.} and Eagar, {Todd N.} and Olaf St{\"u}ve",
year = "2019",
month = "7",
day = "1",
doi = "10.1212/NXI.0000000000000563",
language = "English (US)",
volume = "6",
journal = "Neurology: Neuroimmunology and NeuroInflammation",
issn = "2332-7812",
publisher = "Lippincott Williams and Wilkins Ltd.",
number = "4",

}

RIS

TY - JOUR

T1 - α4-integrin deficiency in B cells does not affect disease in a T-cell-mediated EAE disease model

AU - Hussain, Rehana Z.

AU - Cravens, Petra D.

AU - Miller-Little, William A.

AU - Doelger, Richard

AU - Granados, Valerie

AU - Herndon, Emily

AU - Okuda, Darin T.

AU - Eagar, Todd N.

AU - Stüve, Olaf

PY - 2019/7/1

Y1 - 2019/7/1

N2 - ObjectiveThe goal of this study was to investigate the role of CD 19+ B cells within the brain and spinal cord during CNS autoimmunity in a peptide-induced, primarily T-cell-mediated experimental autoimmune encephalomyelitis (EAE) model of MS. We hypothesized that CD19+ B cells outside the CNS drive inflammation in EAE.MethodsWe generated CD19.Cre+/- α4-integrinfl/fl mice. EAE was induced by active immunization with myelin oligodendrocyte glycoprotein peptide (MOGp35-55). Multiparameter flow cytometry was used to phenotype leukocyte subsets in primary and secondary lymphoid organs and the CNS. Serum cytokine levels and Ig levels were assessed by bead array. B-cell adoptive transfer was used to determine the compartment-specific pathogenic role of antigen-specific and non-antigen-specific B cells.ResultsA genetic ablation of α4-integrin in CD19+/- B cells significantly reduced the number of CD19+ B cells in the CNS but does not affect EAE disease activity in active MOGp35-55-induced disease. The composition of B-cell subsets in the brain, primary lymphoid organs, and secondary lymphoid organs of CD19.Cre+/- α4-integrinfl/fl mice was unchanged during MOGp35-55-induced EAE. Adoptive transfer of purified CD19+ B cells from CD19.Cre+/- α4-integrinfl/fl mice or C57BL/6 wild-type (WT) control mice immunized with recombinant rMOG1-125 or ovalbumin323-339 into MOGp35-55-immunized CD19.Cre+/- α4-integrinfl/fl mice caused worse clinical EAE than was observed in MOGp35-55-immunized C57BL/6 WT control mice that did not receive adoptively transferred CD19+ B cells.ConclusionsObservations made in CD19.Cre+/- α4-integrinfl/fl mice in active MOGp35-55-induced EAE suggest a compartment-specific pathogenic role of CD19+ B cells mostly outside of the CNS that is not necessarily antigen specific.

AB - ObjectiveThe goal of this study was to investigate the role of CD 19+ B cells within the brain and spinal cord during CNS autoimmunity in a peptide-induced, primarily T-cell-mediated experimental autoimmune encephalomyelitis (EAE) model of MS. We hypothesized that CD19+ B cells outside the CNS drive inflammation in EAE.MethodsWe generated CD19.Cre+/- α4-integrinfl/fl mice. EAE was induced by active immunization with myelin oligodendrocyte glycoprotein peptide (MOGp35-55). Multiparameter flow cytometry was used to phenotype leukocyte subsets in primary and secondary lymphoid organs and the CNS. Serum cytokine levels and Ig levels were assessed by bead array. B-cell adoptive transfer was used to determine the compartment-specific pathogenic role of antigen-specific and non-antigen-specific B cells.ResultsA genetic ablation of α4-integrin in CD19+/- B cells significantly reduced the number of CD19+ B cells in the CNS but does not affect EAE disease activity in active MOGp35-55-induced disease. The composition of B-cell subsets in the brain, primary lymphoid organs, and secondary lymphoid organs of CD19.Cre+/- α4-integrinfl/fl mice was unchanged during MOGp35-55-induced EAE. Adoptive transfer of purified CD19+ B cells from CD19.Cre+/- α4-integrinfl/fl mice or C57BL/6 wild-type (WT) control mice immunized with recombinant rMOG1-125 or ovalbumin323-339 into MOGp35-55-immunized CD19.Cre+/- α4-integrinfl/fl mice caused worse clinical EAE than was observed in MOGp35-55-immunized C57BL/6 WT control mice that did not receive adoptively transferred CD19+ B cells.ConclusionsObservations made in CD19.Cre+/- α4-integrinfl/fl mice in active MOGp35-55-induced EAE suggest a compartment-specific pathogenic role of CD19+ B cells mostly outside of the CNS that is not necessarily antigen specific.

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U2 - 10.1212/NXI.0000000000000563

DO - 10.1212/NXI.0000000000000563

M3 - Article

VL - 6

JO - Neurology: Neuroimmunology and NeuroInflammation

T2 - Neurology: Neuroimmunology and NeuroInflammation

JF - Neurology: Neuroimmunology and NeuroInflammation

SN - 2332-7812

IS - 4

M1 - e563

ER -

ID: 51948836