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. 2021 Feb 4;11:623989. doi: 10.3389/fimmu.2020.623989

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Copyright © 2021 Okawa, Nagai and Hase

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Bone marrow serves as a reservoir for several immune cell subsets in response to calorie restriction (CR) or fasting. Under low-energy conditions, naïve B cells, monocytes, and memory CD8⁺ T cells accumulate in the bone marrow. Fasting lowers CXCL13 levels in PPs and reciprocally increases the expression in the bone marrow. This leads to the migration of naïve B cells from PPs to the bone marrow. On the other hand, GC B cells and IgA⁺ B cells undergo apoptosis. Fasting diminishes circulating CCL2 levels through AMPK/PPARα signaling activation. Consequently, the egress of monocytes from the bone marrow is suppressed. Dietary restriction drives CD8⁺ memory T cells to traffic toward the bone marrow in the S1P/S1PR1- and CXCL12/CXCR4-dependent manner. The bone marrow microenvironment provides a tissue-specific niche for the maintenance of memory CD8⁺ T cells with low glucocorticoid concentration and abundant adipocytes.