CNS accumulation of regulatory B cells is VLA-4-dependent

Klaus Lehmann-Horn, Sharon A Sagan, Ryan C Winger, Collin M Spencer, Claude C A Bernard, Raymond A Sobel, Scott S Zamvil

Research output: Contribution to journalArticleResearchpeer-review

Abstract

OBJECTIVE: To investigate the role of very late antigen-4 (VLA-4) on regulatory B cells (Breg) in CNS autoimmune disease. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in mice selectively deficient for VLA-4 on B cells (CD19cre/alpha4(f/f)) by immunization with myelin oligodendrocyte glycoprotein (MOG) peptide (p)35-55 or recombinant human (rh) MOG protein. B-cell and T-cell populations were examined by flow cytometry and immunohistochemistry. Breg were evaluated by intracellular IL-10 staining of B cells and, secondly, by coexpression of CD1d and CD5. RESULTS: As previously reported, EAE was less severe in B-cell VLA-4-deficient vs control CD19cre mice when induced by rhMOG, a model that is B-cell-dependent and leads to efficient B-cell activation and antibody production. Paradoxically, B-cell VLA-4-deficient mice developed more severe clinical disease than control mice when EAE was induced with MOG p35-55, a B-cell-independent encephalitogen that does not efficiently activate B cells. Peripheral T-cell and humoral immune responses were not altered in B-cell VLA-4-deficient mice. In MOG p35-55-induced EAE, B-cell VLA-4 deficiency reduced CNS accumulation of B but not T cells. Breg were detected in the CNS of control mice with MOG p35-55-induced EAE. However, more severe EAE in B-cell VLA-4-deficient mice was associated with virtual absence of CNS Breg. CONCLUSIONS: Our results demonstrate that CNS accumulation of Breg is VLA-4-dependent and suggest that Breg may contribute to regulation of CNS autoimmunity in situ. These observations underscore the need to choose the appropriate encephalitogen when studying how B cells contribute to pathogenesis or regulation of CNS autoimmunity.
Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalNeurology: Neuroimmunology & Neuroinflammation
Volume3
Issue number2
DOIs
Publication statusPublished - 2016

Cite this

Lehmann-Horn, K., Sagan, S. A., Winger, R. C., Spencer, C. M., Bernard, C. C. A., Sobel, R. A., & Zamvil, S. S. (2016). CNS accumulation of regulatory B cells is VLA-4-dependent. Neurology: Neuroimmunology & Neuroinflammation, 3(2), 1-7. https://doi.org/10.1212/NXI.0000000000000212
Lehmann-Horn, Klaus ; Sagan, Sharon A ; Winger, Ryan C ; Spencer, Collin M ; Bernard, Claude C A ; Sobel, Raymond A ; Zamvil, Scott S. / CNS accumulation of regulatory B cells is VLA-4-dependent. In: Neurology: Neuroimmunology & Neuroinflammation. 2016 ; Vol. 3, No. 2. pp. 1-7.
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abstract = "OBJECTIVE: To investigate the role of very late antigen-4 (VLA-4) on regulatory B cells (Breg) in CNS autoimmune disease. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in mice selectively deficient for VLA-4 on B cells (CD19cre/alpha4(f/f)) by immunization with myelin oligodendrocyte glycoprotein (MOG) peptide (p)35-55 or recombinant human (rh) MOG protein. B-cell and T-cell populations were examined by flow cytometry and immunohistochemistry. Breg were evaluated by intracellular IL-10 staining of B cells and, secondly, by coexpression of CD1d and CD5. RESULTS: As previously reported, EAE was less severe in B-cell VLA-4-deficient vs control CD19cre mice when induced by rhMOG, a model that is B-cell-dependent and leads to efficient B-cell activation and antibody production. Paradoxically, B-cell VLA-4-deficient mice developed more severe clinical disease than control mice when EAE was induced with MOG p35-55, a B-cell-independent encephalitogen that does not efficiently activate B cells. Peripheral T-cell and humoral immune responses were not altered in B-cell VLA-4-deficient mice. In MOG p35-55-induced EAE, B-cell VLA-4 deficiency reduced CNS accumulation of B but not T cells. Breg were detected in the CNS of control mice with MOG p35-55-induced EAE. However, more severe EAE in B-cell VLA-4-deficient mice was associated with virtual absence of CNS Breg. CONCLUSIONS: Our results demonstrate that CNS accumulation of Breg is VLA-4-dependent and suggest that Breg may contribute to regulation of CNS autoimmunity in situ. These observations underscore the need to choose the appropriate encephalitogen when studying how B cells contribute to pathogenesis or regulation of CNS autoimmunity.",
author = "Klaus Lehmann-Horn and Sagan, {Sharon A} and Winger, {Ryan C} and Spencer, {Collin M} and Bernard, {Claude C A} and Sobel, {Raymond A} and Zamvil, {Scott S}",
year = "2016",
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language = "English",
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Lehmann-Horn, K, Sagan, SA, Winger, RC, Spencer, CM, Bernard, CCA, Sobel, RA & Zamvil, SS 2016, 'CNS accumulation of regulatory B cells is VLA-4-dependent', Neurology: Neuroimmunology & Neuroinflammation, vol. 3, no. 2, pp. 1-7. https://doi.org/10.1212/NXI.0000000000000212

CNS accumulation of regulatory B cells is VLA-4-dependent. / Lehmann-Horn, Klaus; Sagan, Sharon A; Winger, Ryan C; Spencer, Collin M; Bernard, Claude C A; Sobel, Raymond A; Zamvil, Scott S.

In: Neurology: Neuroimmunology & Neuroinflammation, Vol. 3, No. 2, 2016, p. 1-7.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - CNS accumulation of regulatory B cells is VLA-4-dependent

AU - Lehmann-Horn, Klaus

AU - Sagan, Sharon A

AU - Winger, Ryan C

AU - Spencer, Collin M

AU - Bernard, Claude C A

AU - Sobel, Raymond A

AU - Zamvil, Scott S

PY - 2016

Y1 - 2016

N2 - OBJECTIVE: To investigate the role of very late antigen-4 (VLA-4) on regulatory B cells (Breg) in CNS autoimmune disease. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in mice selectively deficient for VLA-4 on B cells (CD19cre/alpha4(f/f)) by immunization with myelin oligodendrocyte glycoprotein (MOG) peptide (p)35-55 or recombinant human (rh) MOG protein. B-cell and T-cell populations were examined by flow cytometry and immunohistochemistry. Breg were evaluated by intracellular IL-10 staining of B cells and, secondly, by coexpression of CD1d and CD5. RESULTS: As previously reported, EAE was less severe in B-cell VLA-4-deficient vs control CD19cre mice when induced by rhMOG, a model that is B-cell-dependent and leads to efficient B-cell activation and antibody production. Paradoxically, B-cell VLA-4-deficient mice developed more severe clinical disease than control mice when EAE was induced with MOG p35-55, a B-cell-independent encephalitogen that does not efficiently activate B cells. Peripheral T-cell and humoral immune responses were not altered in B-cell VLA-4-deficient mice. In MOG p35-55-induced EAE, B-cell VLA-4 deficiency reduced CNS accumulation of B but not T cells. Breg were detected in the CNS of control mice with MOG p35-55-induced EAE. However, more severe EAE in B-cell VLA-4-deficient mice was associated with virtual absence of CNS Breg. CONCLUSIONS: Our results demonstrate that CNS accumulation of Breg is VLA-4-dependent and suggest that Breg may contribute to regulation of CNS autoimmunity in situ. These observations underscore the need to choose the appropriate encephalitogen when studying how B cells contribute to pathogenesis or regulation of CNS autoimmunity.

AB - OBJECTIVE: To investigate the role of very late antigen-4 (VLA-4) on regulatory B cells (Breg) in CNS autoimmune disease. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in mice selectively deficient for VLA-4 on B cells (CD19cre/alpha4(f/f)) by immunization with myelin oligodendrocyte glycoprotein (MOG) peptide (p)35-55 or recombinant human (rh) MOG protein. B-cell and T-cell populations were examined by flow cytometry and immunohistochemistry. Breg were evaluated by intracellular IL-10 staining of B cells and, secondly, by coexpression of CD1d and CD5. RESULTS: As previously reported, EAE was less severe in B-cell VLA-4-deficient vs control CD19cre mice when induced by rhMOG, a model that is B-cell-dependent and leads to efficient B-cell activation and antibody production. Paradoxically, B-cell VLA-4-deficient mice developed more severe clinical disease than control mice when EAE was induced with MOG p35-55, a B-cell-independent encephalitogen that does not efficiently activate B cells. Peripheral T-cell and humoral immune responses were not altered in B-cell VLA-4-deficient mice. In MOG p35-55-induced EAE, B-cell VLA-4 deficiency reduced CNS accumulation of B but not T cells. Breg were detected in the CNS of control mice with MOG p35-55-induced EAE. However, more severe EAE in B-cell VLA-4-deficient mice was associated with virtual absence of CNS Breg. CONCLUSIONS: Our results demonstrate that CNS accumulation of Breg is VLA-4-dependent and suggest that Breg may contribute to regulation of CNS autoimmunity in situ. These observations underscore the need to choose the appropriate encephalitogen when studying how B cells contribute to pathogenesis or regulation of CNS autoimmunity.

UR - http://www.ncbi.nlm.nih.gov/pubmed/27027096

U2 - 10.1212/NXI.0000000000000212

DO - 10.1212/NXI.0000000000000212

M3 - Article

VL - 3

SP - 1

EP - 7

JO - Neurology: Neuroimmunology & Neuroinflammation

JF - Neurology: Neuroimmunology & Neuroinflammation

SN - 2332-7812

IS - 2

ER -