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

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

Research output: Contribution to journalArticle

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.

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

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Integrins
Autoimmune Diseases
B-Lymphocytes
Autoimmune Experimental Encephalomyelitis
T-Lymphocytes
Adoptive Transfer
Myelin-Oligodendrocyte Glycoprotein
B-Lymphocyte Subsets
Antigens
Peptides
Brain
Autoimmunity
Inbred C57BL Mouse
Spinal Cord
Flow Cytometry
Vaccination
Leukocytes
Cytokines
Inflammation
Phenotype

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

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

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.
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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.",
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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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