期刊
FRONTIERS IN IMMUNOLOGY
卷 10, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2019.00534
关键词
integrins; LFA-1; VLA-4; memory B cells; adhesion; spleen; autoimmunity
类别
资金
- Swedish Science Research Council [2018-03128]
- Swedish Cancer Foundation [CAN 2016/481]
- Swedish Childhood Cancer Fund [PR2018-0170]
- AFA
- ALF: the regional agreement on medical training and clinical research
- King Gustav V. Stiftelse
- Arne Lundbergs Forskningsstiftelse
- Swedish Medical Society
- Swedish Rheumatism Association [R-758881]
- Stiftelsen Lars Hiertas minne
- Lundgrens Stiftelse
- Amlovs Stiftelser
- Adlerbertska stiftelsen
- Royal Society of Arts and Sciences in Gothenburg
- Sigurd och Elsa Golje's minne
- Swedish Research Council [2018-03128] Funding Source: Swedish Research Council
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 naive 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, naive B and MBCs of patients receiving anti-TNF medication have enhanced levels of the active form of LFA-1. Commensurate levels of the active alpha L 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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