Dissecting Integrin Expression and Function on Memory B Cells in Mice and Humans in Autoimmunity

Alessandro Camponeschi, Natalija Gerasimcik, Ying Wang, Timothy Fredriksson, Dongfeng Chen, Chiara Farroni, Katrin Thorarinsdottir, Louise Sjökvist Ottsjö, Alaitz Aranburu, Susanna Cardell, Rita Carsetti, Inger Gjertsson, Inga-Lill Mårtensson, Ola Grimsholm

Research output: Contribution to journalArticle

Abstract

Immunological memory ensures life-long protection against previously encountered pathogens, and in mice and humans the spleen is an important reservoir for long-lived memory B cells (MBCs). It is well-established that integrins play several crucial roles in lymphocyte survival and trafficking, but their involvement in the retention of MBCs in secondary lymphoid organs, and differences between B cell subsets in their adhesion capacity to ICAM-1 and/or VCAM-1 have not yet been confirmed. Here, we use an autoimmune mouse model, where MBCs are abundant, to show that the highest levels of LFA-1 and VLA-4 amongst B cells are found on MBCs. In vivo blockade of VLA-4 alone or in combination with LFA-1, but not LFA-1 alone, causes a release of MBCs from the spleen into the blood stream. In humans, we find that in peripheral blood, spleens, and tonsils from healthy donors the highest expression levels of the integrins LFA-1 and VLA-4 are also found on MBCs. Consistent with this, we found MBCs to have a higher capacity to adhere to ICAM-1 and VCAM-1 than naïve B cells. In patients with the autoimmune disease rheumatoid arthritis, it is the MBCs that have the highest levels of LFA-1 and VLA-4; moreover, compared with healthy donors, naïve B and MBCs of patients receiving anti-TNF medication have enhanced levels of the active form of LFA-1. Commensurate levels of the active αL subunit can be induced on B cells from healthy donors by exposure to the integrin ligands. Thus, our findings establish the selective use of the integrins LFA-1 and VLA-4 in the localization and adhesion of MBCs in both mice and humans.

Original languageEnglish
Pages (from-to)534
JournalFrontiers in Immunology
Volume10
DOIs
Publication statusPublished - Mar 21 2019

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Autoimmunity
Integrins
B-Lymphocytes
Lymphocyte Function-Associated Antigen-1
Integrin alpha4beta1
Spleen
Vascular Cell Adhesion Molecule-1
Tissue Donors
Intercellular Adhesion Molecule-1
Immunologic Memory
B-Lymphocyte Subsets
Palatine Tonsil
Autoimmune Diseases
Rheumatoid Arthritis
Lymphocytes
Ligands

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Dissecting Integrin Expression and Function on Memory B Cells in Mice and Humans in Autoimmunity. / Camponeschi, Alessandro; Gerasimcik, Natalija; Wang, Ying; Fredriksson, Timothy; Chen, Dongfeng; Farroni, Chiara; Thorarinsdottir, Katrin; Sjökvist Ottsjö, Louise; Aranburu, Alaitz; Cardell, Susanna; Carsetti, Rita; Gjertsson, Inger; Mårtensson, Inga-Lill; Grimsholm, Ola.

In: Frontiers in Immunology, Vol. 10, 21.03.2019, p. 534.

Research output: Contribution to journalArticle

Camponeschi, A, Gerasimcik, N, Wang, Y, Fredriksson, T, Chen, D, Farroni, C, Thorarinsdottir, K, Sjökvist Ottsjö, L, Aranburu, A, Cardell, S, Carsetti, R, Gjertsson, I, Mårtensson, I-L & Grimsholm, O 2019, 'Dissecting Integrin Expression and Function on Memory B Cells in Mice and Humans in Autoimmunity', Frontiers in Immunology, vol. 10, pp. 534. https://doi.org/10.3389/fimmu.2019.00534
Camponeschi, Alessandro ; Gerasimcik, Natalija ; Wang, Ying ; Fredriksson, Timothy ; Chen, Dongfeng ; Farroni, Chiara ; Thorarinsdottir, Katrin ; Sjökvist Ottsjö, Louise ; Aranburu, Alaitz ; Cardell, Susanna ; Carsetti, Rita ; Gjertsson, Inger ; Mårtensson, Inga-Lill ; Grimsholm, Ola. / Dissecting Integrin Expression and Function on Memory B Cells in Mice and Humans in Autoimmunity. In: Frontiers in Immunology. 2019 ; Vol. 10. pp. 534.
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AU - Camponeschi, Alessandro

AU - Gerasimcik, Natalija

AU - Wang, Ying

AU - Fredriksson, Timothy

AU - Chen, Dongfeng

AU - Farroni, Chiara

AU - Thorarinsdottir, Katrin

AU - Sjökvist Ottsjö, Louise

AU - Aranburu, Alaitz

AU - Cardell, Susanna

AU - Carsetti, Rita

AU - Gjertsson, Inger

AU - Mårtensson, Inga-Lill

AU - Grimsholm, Ola

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N2 - Immunological memory ensures life-long protection against previously encountered pathogens, and in mice and humans the spleen is an important reservoir for long-lived memory B cells (MBCs). It is well-established that integrins play several crucial roles in lymphocyte survival and trafficking, but their involvement in the retention of MBCs in secondary lymphoid organs, and differences between B cell subsets in their adhesion capacity to ICAM-1 and/or VCAM-1 have not yet been confirmed. Here, we use an autoimmune mouse model, where MBCs are abundant, to show that the highest levels of LFA-1 and VLA-4 amongst B cells are found on MBCs. In vivo blockade of VLA-4 alone or in combination with LFA-1, but not LFA-1 alone, causes a release of MBCs from the spleen into the blood stream. In humans, we find that in peripheral blood, spleens, and tonsils from healthy donors the highest expression levels of the integrins LFA-1 and VLA-4 are also found on MBCs. Consistent with this, we found MBCs to have a higher capacity to adhere to ICAM-1 and VCAM-1 than naïve B cells. In patients with the autoimmune disease rheumatoid arthritis, it is the MBCs that have the highest levels of LFA-1 and VLA-4; moreover, compared with healthy donors, naïve B and MBCs of patients receiving anti-TNF medication have enhanced levels of the active form of LFA-1. Commensurate levels of the active αL subunit can be induced on B cells from healthy donors by exposure to the integrin ligands. Thus, our findings establish the selective use of the integrins LFA-1 and VLA-4 in the localization and adhesion of MBCs in both mice and humans.

AB - Immunological memory ensures life-long protection against previously encountered pathogens, and in mice and humans the spleen is an important reservoir for long-lived memory B cells (MBCs). It is well-established that integrins play several crucial roles in lymphocyte survival and trafficking, but their involvement in the retention of MBCs in secondary lymphoid organs, and differences between B cell subsets in their adhesion capacity to ICAM-1 and/or VCAM-1 have not yet been confirmed. Here, we use an autoimmune mouse model, where MBCs are abundant, to show that the highest levels of LFA-1 and VLA-4 amongst B cells are found on MBCs. In vivo blockade of VLA-4 alone or in combination with LFA-1, but not LFA-1 alone, causes a release of MBCs from the spleen into the blood stream. In humans, we find that in peripheral blood, spleens, and tonsils from healthy donors the highest expression levels of the integrins LFA-1 and VLA-4 are also found on MBCs. Consistent with this, we found MBCs to have a higher capacity to adhere to ICAM-1 and VCAM-1 than naïve B cells. In patients with the autoimmune disease rheumatoid arthritis, it is the MBCs that have the highest levels of LFA-1 and VLA-4; moreover, compared with healthy donors, naïve B and MBCs of patients receiving anti-TNF medication have enhanced levels of the active form of LFA-1. Commensurate levels of the active αL subunit can be induced on B cells from healthy donors by exposure to the integrin ligands. Thus, our findings establish the selective use of the integrins LFA-1 and VLA-4 in the localization and adhesion of MBCs in both mice and humans.

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JO - Frontiers in Immunology

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