Mesenchymal lineage cells and their importance in B lymphocyte niches

Abstract

Early B lymphopoiesis occurs in the bone marrow and is reliant on interactions with numerous cell types in the bone marrow microenvironment, particularly those of the mesenchymal lineage. Each cellular niche that supports the distinct stages of B lymphopoiesis is unique. Different cell types and signaling molecules are important for the progressive stages of B lymphocyte differentiation. Cells expressing CXCL12 and IL-7 have long been recognized as having essential roles in facilitating progression through stages of B lymphopoiesis. Recently, a number of other factors that extrinsically mediate B lymphopoiesis (positively or negatively) have been identified. In addition, the use of transgenic mouse models to delete specific genes in mesenchymal lineage cells has further contributed to our understanding of how B lymphopoiesis is regulated in the bone marrow. This review will cover the current understanding of B lymphocyte niches in the bone marrow and key extrinsic molecules and signaling pathways involved in these niches, with a focus on how mesenchymal lineage cells regulate B lymphopoiesis.

Regulation of Energy Metabolism during Early B Lymphocyte Development

“…They are derived from pluripotent stem cells and develop through the following stages: hematopoietic stem cells (HSCs); common lymphoid progenitors (CLPs); B cell-biased lymphoid progenitors (BLPs); and pre-pro-, pro- and pre-B cells. B cell precursors require cell contact and specific niches in the BM for their survival and growth [1]. Proliferative HSC and pre-pro-B cells, the earliest committed B lymphocyte progenitors, develop in the vicinity of sinusoids [2,3,4].…”

“…Pre-pro-B cells localize next to CXCL12 (also: SDF-1, stromal cell derived factor)-abundant reticular (CAR) cells, whereas pro-B cells are found adjacent to IL-7-expressing stromal cells, the majority of which are in close contact with the vasculature [5]. Pre-B cells localize near Galectin-1-expressing cells [1]. Each of these different niches possesses different oxygen tensions, indicating that there is a need to adapt mitochondrial respiration during different B cell developmental stages [6].…”

“…The active migration of cells towards their respective niches is induced by chemokines such as CXCL12 [3,5]. CXCL12 and CXCR4, the only receptor for CXCL12, are required for HSC and B cell development in a non-redundant manner [1,7,8,9], with CXCL12 eliciting an intracellular Ca 2+ signal [7]. The first step of B lymphocyte development is controlled by the transcription factors (TFs) PU.1 and Ikaros (IKZF1), both of which are expressed in CLPs.…”

“…Progenitors then commit to the B cell lineage by expressing E2A, EBF-1 and Pax-5 (reviewed in [10]). Pre-pro-B cells develop into pro-B cells (Figure 1), in which proliferation is supported by numerous factors, especially the cytokine interleukin 7 (IL-7) as well as CXCL12 and stem cell factor (SCF) [1]. Another important factor supporting early B cell development is Fms-like tyrosine kinase (Flt) 3 ligand [1].…”

“…Pre-pro-B cells develop into pro-B cells (Figure 1), in which proliferation is supported by numerous factors, especially the cytokine interleukin 7 (IL-7) as well as CXCL12 and stem cell factor (SCF) [1]. Another important factor supporting early B cell development is Fms-like tyrosine kinase (Flt) 3 ligand [1]. B lymphocyte development follows defined stages that can be distinguished by the expression of cell surface markers, genetic rearrangements of Immunoglobulin (Ig) heavy and light chain loci and cell size and mitotic activity [11] (Figure 1; for detailed reviews see [1,12,13,14]).…”