Galectin-1–expressing stromal cells constitute a specific niche for pre-BII cell development in mouse bone marrow

Abstract

In the bone marrow (BM), stromal cells constitute a supportive tissue indispensable for the generation of pro-B/pre-BI, pre-BII, and immature B lymphocytes. IL-7-producing stromal cells constitute a cellular niche for pro-B/pre-BI cells, but no specific stromal cell microenvironment was identified for pre-BII cells expressing a functional pre-B cell receptor (pre-BCR). However expression of the pre-BCR represents a crucial checkpoint during B-cell development. We recently demonstrated that the stromal cell derived-galectin1 (GAL1) is a ligand for the pre-BCR, involved in the proliferation and differentiation of normal mouse pre-BII cells. Here we show that nonhematopoietic osteoblasts and reticular cells in the BM express GAL1. We observed that pre-BII cells, unlike the other B-cell subsets, were specifically localized in close contact with GAL1 ؉ reticular cells. We also determined that IL-7 ؉ and GAL1 ؉ cells represent 2 distinct mesenchymal populations with different BM localization. These results demonstrate the existence of a pre-BII specific stromal cell niche and indicate that early B cells move from IL-7 ؉ to GAL1 ؉ supportive BM niches during their development. (Blood. 2011; 117(24):6552-6561) IntroductionThe bone marrow (BM) is the primary site of hematopoiesis after birth. Hematopoietic stem cells (HSCs) and hematopoietic progenitors are located in close contact with a special stromal microenvironment, known as niches, composed of mesenchymal cells, osteoblasts, endothelial cells, and adipocytes, indispensable for their differentiation. 1,2 Recent reports indicate that the spatial repartition of BM stromal cells and hematopoietic progenitors follows a coordinated regulation. 3 HSCs are in contact with osteoblasts on bone surfaces and endothelial cells lining sinusoids, and move near CXCL12 ϩ reticular stromal cells while they differentiate. In this tissue, B-cell differentiation is also a highly regulated process, which generates widely diversified immature B cells tolerant to self. Stage-specific cellular niches have been identified for the first steps of the B lymphopoiesis. 2 The earliest B220 ϩ cKit ϩ pro-B/pre-BI cells undergoing immunoglobulin H (IgH) gene rearrangements locate near IL-7-producing stromal cells. At the next step, when a functional Ig chain is produced and associated with the surrogate light chain (SLC) composed of 5 and VpreB and with the CD79a/CD79b signaling complex, the pre-B-cell receptor (pre-BCR) is formed and expressed at the surface of pre-BII cells. At this stage, cells leave IL-7-expressing stromal cells, but no specific pre-BII cellular niche has yet been identified. 3 Expression of the pre-BCR represents a crucial checkpoint during B-cell development as this receptor controls pre-BII-cell development and the selection of the Ig repertoire. 4 The galectin-1 (GAL1) lectin and heparan sulfates, produced by the BM microenvironment, have been reported to bind to the pre-BCR, [5][6][7] and GAL1 was shown to promote pre-BCR clustering and signaling. 5 GAL1 binds to the SLC ...

Pre-B cell receptor binding to galectin-1 modifies galectin-1/carbohydrate affinity to modulate specific galectin-1/glycan lattice interactions

“…Indeed, it has been shown that pre-BII cells are not able to contact stromal cells that are not secreting GAL1 (ref. 21). The significant LacNAc content of pre-BII cells is therefore an important determinant for cell recognition and cell niche specificity.…”

“…Expression of the pre-B cell receptor (pre-BCR) represents a crucial checkpoint during B-cell development as this receptor controls pre-BII cell development and the selection of the Igm repertoire 23 . We have found that pre-BII cells are associated to medullar stromal cells secreting GAL1 that constitute a specific pre-BII cell niche in the bone marrow 21 . At the contact zone between pre-BII and stromal cells, GAL1, preBCRs and glycosylated integrins relocalize 18 .…”

“…We previously evidenced a crucial role of GAL1 in B-cell development through the formation of a GAL1-dependent lattice between pre-BII and stromal cells [18][19][20][21] . B cells are generated from haematopoietic stem cells and develop in the bone marrow before they migrate into the blood to reach peripheral lymphoid organs.…”

JAM-B regulates maintenance of hematopoietic stem cells in the bone marrow

“…Immunohistochemistry was performed as previously described. 7,19,30 Briefly, 20-mm-thick sections were transferred to adhesive-coated slides with the CryoJane Tape-Transfer system according to the manufacturer's protocol (Instrumedics). Bone sections (after fixation in methanol) were incubated for 1 hour at room temperature with a blocking solution (PBS, 2% BSA, 1% donkey serum, 1% FCS).…”

Synergistic Induction of Galectin-1 by CCAAT/Enhancer Binding Protein α and Hypoxia-inducible Factor 1α and Its Role in Differentiation of Acute Myeloid Leukemic Cells

“…Galectin-1 has been found to be differentially expressed in various normal and pathological tissues and to mediate a series of signal pathways involving cellular adhesion, migration, proliferation, differentiation, and death (3)(4)(5)(6). For example, the mesenchymal stem cells of the bone marrow highly express galectin-1 protein (7,8), and galectin-1-expressing stromal cells constitute a specific niche for pre-BII cell development in mice (9). Upon erythroid differentiation of leukemic K562 cells, the galectin-1 is externalized and bound to the cell surface (10).…”