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

Artikel i vetenskaplig tidskrift
Författare 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
Publicerad i Frontiers in immunology
Volym 10
Sidor 534
ISSN 1664-3224
Publiceringsår 2019
Publicerad vid Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning
Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi
Sidor 534
Språk en
Länkar dx.doi.org/10.3389/fimmu.2019.00534
www.ncbi.nlm.nih.gov/entrez/query.f...
Ämneskategorier Cell- och molekylärbiologi, Immunbiologi

Sammanfattning

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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