Dietary Restriction and Fasting Arrest B and T Cell Development and Increase Mature B and T Cell Numbers in Bone Marrow

Abstract

Dietary restriction (DR) delays ageing and extends life span. Both long- and short-term DR, as well as short-term fasting provide robust protection against many “neuronal and surgery related damaging phenomena” such as Parkinson’s disease and ischemia-reperfusion injury. The exact mechanism behind this phenomenon has not yet been elucidated. Its anti-inflammatory actions prompted us to thoroughly investigate the consequences of DR and fasting on B and T cell compartments in primary and secondary lymphoid organs of male C57Bl/6 mice. In BM we found that DR and fasting cause a decrease in the total B cell population and arrest early B cell development, while increasing the number of recirculating mature B cells. In the fasting group, a significant reduction in peripheral B cell counts was observed in both spleen and mesenteric lymph nodes (mLN). Thymopoiesis was arrested significantly at double negative DN2 stage due to fasting, whereas DR resulted in a partial arrest of thymocyte development at the DN4 stage. Mature CD3+ T cell populations were increased in BM and decreased in both spleen and mLN. Thus, DR arrests B cell development in the BM but increases the number of recirculating mature B cells. DR also arrests maturation of T cells in thymus, resulting in depletion of mature T cells from spleen and mLN while recruiting them to the BM. The functional relevance in relation to protection against organ damage needs to be determined.

Short-Term Fasting Induces Cell Cycle Arrest in Immature Hematopoietic Cells and Increases the Number of Naïve T Cells in the Bone Marrow of Mice

“…This result is congruent with previous reports [18, 19] and one possible reason for B cell decrease is inhibition of B cell differentiation in the BM during fasting [18]. …”

AIF loss deregulates hematopoiesis and reveals different adaptive metabolic responses in bone marrow cells and thymocytes

“…Indeed, the blockade at the DN stage observed in our AIF −/Y mice, with alterations in the DN1, DN2, and DN3 stages, cannot be detected in the Lck-Cre animals. Of note, the adjustment in the mitochondrial metabolism profoundly alters DN1to-DN4 thymocyte development [9,10]. Remarkably, in contrast to previous results on Hq and CD19-Cre AIF KO mouse models [26][27][28], our findings originally indicated that the loss of AIF undoubtedly affected B-cell and erythrocyte development.…”

“…Concerning thymopoiesis, less is known about the OXPHOS implication in the differentiation of double negative (DN) progenitor cells. However, a fine-tuning between ROS and glycolytic activation appears important for DN1-to-DN4 transitions [9,10]. Apoptosis-inducing factor (AIF), a Janus mitochondrial protein that is encoded by the Aifm1 (Aif, Pdcd8) gene on the X-chromosome, has been implicated in maintaining mitochondrial electron transport chain (ETC) function [11][12][13][14].…”

Response of mouse thymic cells to radiation after transfusion of mesenchymal stem cells

“…It has been shown that mouse thymus T cells are derived from the bone marrow, [27] they migrate in different parts of the thymus gland to differentiate and mature, and are released into the blood for immune response. Most studies suggest that immature thymus T cells normally develop into T cell lymphoma continuously, when CD4-/CD8- T cells are differentiated into CD4+/CD8- T cells and CD4-/CD8+ T cells from CD4+/CD8+ T cells.…”