Genesis of B lymphocytes in the bone marrow: Extravascular and intravascular localization of surface IgM‐bearing cells in mouse bone marrow detected by electron‐microscope radioautography after in vivo perfusion of ¹²⁵I anti‐IgM antibody

Abstract

The role of mammalian bone marrow in generating surface IgM (sIgM)-bearing B lymphocytes is reviewed. Precursor cells in the marrow give rise to large, rapidly dividing cells bearing free cytoplasmic mu chains (c mu). The progeny of the large c mu+ cells form a population of small, nondividing c mu+ cells that mature into small lymphocytes, progressively expressing sIgM and other B-cell surface membrane components. Newly formed sIgM+ cells soon migrate through the bloodstream to the spleen and other lymphoid tissues, where they may die after a short lifespan or be activated to produce antibody molecules. The large-scale lymphocytopoiesis in the bone marrow thus maintains a population of rapidly renewed virgin B lymphocytes in the peripheral lymphoid tissues. This process continuously creates and selects B cell clones with the wide range of antibody specificities necessary to mediate primary humoral immune responses through postnatal life. A technique for perfusing radiolabeled anti-IgM antibodies in young mice has now permitted sIgM+ cells to be detected radioautographically in histological preparations of bone marrow under the electron microscope. Small sIgM+ lymphocytes are situated either singly or in small groups throughout the extravascular hemopoietic compartment of the bone marrow, often near sinusoid walls adjacent to late erythroblasts and reticular cells. Some regional concentrations of sIgM+ cells are apparent. sIgM+ cells also appear in transit through the sinusoidal endothelium and are markedly concentrated in the lumen of some sinusoids. Intrasinusoidal sIgM+ small lymphocytes have high densities of sIgM and long microvilli, on which sIgM molecules are concentrated. These studies reveal the localization and cell associations of specifically identified sIgM+ small lymphocytes in the extravascular marrow compartment and suggest that these cells may also undergo a transient intravascular storage and maturation phase. Use of this in vivo immunolabeling technique to detect other cell-surface markers may further elucidate the microenvironmental basis of B lymphocyte genesis in the bone marrow.

Bone Marrow Endothelial Cells Induce Immature and Mature B Cell Egress in Response to Erythropoietin

“…For example, hematopoietic stem cells (HSCs) reside near blood vasculature, where they interact with stem cell niche cells such as perivascular cells (Mendelson and Frenette, 2014;Morrison and Scadden, 2014). Immature B cells are retained in the perivascular parenchymal area and inside sinusoids to undergo negative selection before exiting the bone marrow Osmond and Batten, 1984;Pereira et al, 2009). Recirculating mature B cells traverse the sinusoidal vasculature to locate in the perivascular area, where they receive survival signals from perivascular dendritic cells (Cariappa et al, 2005;Sapoznikov et al, 2008).…”

The sphingosine-1-phosphate transporter Spns2 expressed on endothelial cells regulates lymphocyte trafficking in mice

“…Thus, these results reveal for what we believe is the first time that ECs are the major cellular source of S1P necessary for the egress of immature B cells from the bone marrow. In the late stage of B cell development in the bone marrow, newly generated immature B cells placed in the parenchyma are first recruited into the sinusoidal compartment and subsequently exported into the peripheral blood (50)(51)(52). Sinusoidal entry of immature B cells is thought to be a key step in bone marrow egress.…”

Inflammation rapidly reorganizes mouse bone marrow B cells and their environment in conjunction with early IgM responses

“…4 The sinusoids themselves represent a niche supportive of B-cell survival and immature B cells load inside sinusoids before leaving for the periphery. 5,6 These sinusoids, and adjacent architecture, support a sizable population of "recirculating" B cells composed of naive immunoglobulin D 1 (IgD 1 ) mature cells. The majority of this population are cells that passed through splenic maturation whereas roughly a third completed development within the bone marrow itself.…”