scholarly journals S1P1 receptor directs the release of immature B cells from bone marrow into blood

2010 ◽  
Vol 207 (5) ◽  
pp. 1113-1124 ◽  
Author(s):  
Maria L. Allende ◽  
Galina Tuymetova ◽  
Bridgin G. Lee ◽  
Eliana Bonifacino ◽  
Yun-Ping Wu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Receptor Gene ◽  
Receptor Expression ◽  
Negative Regulator ◽  
S1p1 Receptor ◽  
Cxcr4 Signaling ◽  
B Cell Maturation ◽  
Immature B Cells

S1P1 receptor expression is required for the egress of newly formed T cells from the thymus and exit of mature T and B cells from secondary lymphoid organs. In this study, we deleted the expression of the S1P1 receptor gene (S1pr1) in developing B cells in the bone marrow. Although B cell maturation within the bone marrow was largely normal in the B cell–specific S1pr1 knockout (B-S1pr1KO) mice, their newly generated immature B cells appeared in the blood at abnormally low numbers as compared with control mice. In the bone marrow of B-S1pr1KO mice, immature B cells in contact with the vascular compartment displayed increased apoptosis as compared with control mice. Forced expression of CD69, a negative regulator of S1P1 receptor expression, in developing bone marrow B cells also reduced the number of immature B cells in the blood. Attenuation of CXCR4 signaling, which is required for the proper retention of developing B cells in bone marrow, did not release immature B cells into the blood of B-S1pr1KO mice as effectively as in control mice. Our results indicate that the S1P1 receptor provides a signal necessary for the efficient transfer of newly generated immature B cells from the bone marrow to the blood.

scholarly journals Prolactin Levels Correlate with Abnormal B Cell Maturation in MRL and MRL/lpr Mouse Models of Systemic Lupus Erythematosus-Like Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Maria Victoria Legorreta-Haquet ◽  
Rocio Flores-Fernández ◽  
Francisco Blanco-Favela ◽  
Ezequiel M Fuentes-Pananá ◽  
Luis Chávez-Sánchez ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Receptor Expression ◽  
Cell Maturation ◽  
B Cell Maturation ◽  
Immature B Cells ◽  
Immature Cells

Prolactin (PRL) plays an important role in modulating the immune response. In B cells, PRL enhances antibody production, including antibodies with self-specificity. In this study, our aims were to determine the level of PRL receptor expression during bone-marrow B-cell development and to assess whether the presence of high PRL serum concentrations influences absolute numbers of developing populations and disease outcome in lupus-prone murine models. We observed that the PRL-receptor is expressed in early bone-marrow B-cell; the expression in lupus-prone mice, which had the highest level of expression in pro-B cells and immature cells, differed from that in wild-type mice. These expression levels did not significantly change in response to hyperprolactinemia; however, populations of pro-B and immature cells from lupus-prone strains showed a decrease in the absolute numbers of cells with high PRL-receptor expression in response to PRL. Because immature self-reactive B cells are constantly being eliminated, we assessed the expression of survival factor BIRC5, which is more highly expressed in both pro-B and immature B-cells in response to PRL and correlates with the onset of disease. These results identify an important role of PRL in the early stages of the B-cell maturation process: PRL may promote the survival of self-reactive clones.

scholarly journals B lymphocytes express and lose syndecan at specific stages of differentiation.

1989 ◽  
Vol 1 (1) ◽  
pp. 27-35 ◽  
Author(s):  
R D Sanderson ◽  
P Lalor ◽  
M Bernfield
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
B Lymphocyte ◽  
Plasma Cells ◽  
Receptor Expression ◽  
Cell Stage ◽  
Precursor B Cells

Lymphopoietic cells require interactions with bone marrow stroma for normal maturation and show changes in adhesion to matrix during their differentiation. Syndecan, a heparan sulfate-rich integral membrane proteoglycan, functions as a matrix receptor by binding cells to interstitial collagens, fibronectin, and thrombospondin. Therefore, we asked whether syndecan was present on the surface of lymphopoietic cells. In bone marrow, we find syndecan only on precursor B cells. Expression changes with pre-B cell maturation in the marrow and with B-lymphocyte differentiation to plasma cells in interstitial matrices. Syndecan on B cell precursors is more heterogeneous and slightly larger than on plasma cells. Syndecan 1) is lost immediately before maturation and release of B lymphocytes into the circulation, 2) is absent on circulating and peripheral B lymphocytes, and 3) is reexpressed upon their differentiation into immobilized plasma cells. Thus, syndecan is expressed only when and where B lymphocytes associate with extracellular matrix. These results indicate that B cells differentiating in vivo alter their matrix receptor expression and suggest a role for syndecan in B cell stage-specific adhesion.

scholarly journals Reduced receptor editing in lupus-prone MRL/lpr mice

2007 ◽  
Vol 204 (12) ◽  
pp. 2853-2864 ◽  
Author(s):  
Jennifer L. Lamoureux ◽  
Lisa C. Watson ◽  
Marie Cherrier ◽  
Patrick Skog ◽  
David Nemazee ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Messenger Rna ◽  
Immunoglobulin M ◽  
Considerable Proportion ◽  
Receptor Editing ◽  
Cell Tolerance ◽  
B Cell Tolerance ◽  
Immature B Cells

The initial B cell repertoire contains a considerable proportion of autoreactive specificities. The first major B cell tolerance checkpoint is at the stage of the immature B cell, where receptor editing is the primary mode of eliminating self-reactivity. The cells that emigrate from the bone marrow have a second tolerance checkpoint in the transitional compartment in the spleen. Although it is known that the second checkpoint is defective in lupus, it is not clear whether there is any breakdown in central B cell tolerance in the bone marrow. We demonstrate that receptor editing is less efficient in the lupus-prone strain MRL/lpr. In an in vitro system, when receptor-editing signals are given to bone marrow immature B cells by antiidiotype antibody or after in vivo exposure to membrane-bound self-antigen, MRL/lpr 3-83 transgenic immature B cells undergo less endogenous rearrangement and up-regulate recombination activating gene messenger RNA to a lesser extent than B10 transgenic cells. CD19, along with immunoglobulin M, is down-regulated in the bone marrow upon receptor editing, but the extent of down-regulation is fivefold less in MRL/lpr mice. Less efficient receptor editing could allow some autoreactive cells to escape from the bone marrow in lupus-prone mice, thus predisposing to autoimmunity.

scholarly journals Regulated Expression of Human Histocompatibility Leukocyte Antigen (HLA)-DO During Antigen-dependent and Antigen-independent Phases of B Cell Development

2002 ◽  
Vol 195 (8) ◽  
pp. 1053-1062 ◽  
Author(s):  
Xinjian Chen ◽  
Oskar Laur ◽  
Taku Kambayashi ◽  
Shiyong Li ◽  
Robert A. Bray ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Peripheral Blood ◽  
Class Ii ◽  
Cell Development ◽  
B Cell Development ◽  
Negative Regulator ◽  
Leukocyte Antigen ◽  
Peptide Loading

Human histocompatibility leukocyte antigen (HLA)-DO, a lysosomal resident major histocompatibility complex class II molecule expressed in B cells, has previously been shown to be a negative regulator of HLA-DM peptide loading function. We analyze the expression of DO in human peripheral blood, lymph node, tonsil, and bone marrow to determine if DO expression is modulated in the physiological setting. B cells, but not monocytes or monocyte-derived dendritic cells, are observed to express this protein. Preclearing experiments demonstrate that ∼50% of HLA-DM is bound to DO in peripheral blood B cells. HLA-DM and HLA-DR expression is demonstrated early in B cell development, beginning at the pro-B stage in adult human bone marrow. In contrast, DO expression is initiated only after B cell development is complete. In all situations, there is a striking correlation between intracellular DO expression and cell surface class II–associated invariant chain peptide expression, which suggests that DO substantially inhibits DM function in primary human B cells. We report that the expression of DO is markedly downmodulated in human germinal center B cells. Modulation of DO expression may provide a mechanism to regulate peptide loading activity and antigen presentation by B cells during the development of humoral immune responses.

SDF-1 Responsiveness Does Not Correlate With CXCR4 Expression Levels of Developing Human Bone Marrow B Cells

Blood ◽  
1999 ◽  
Vol 94 (9) ◽  
pp. 2990-2998 ◽  
Author(s):  
Marek Honczarenko ◽  
Raymond S. Douglas ◽  
Clarissa Mathias ◽  
Benhur Lee ◽  
Mariusz Z. Ratajczak ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Cxcr4 Expression ◽  
B Lymphopoiesis ◽  
Cell Stage ◽  
Immature B Cells ◽  
Stromal Cell Derived Factor ◽  
And Migration ◽  
And Function

Abstract Chemokines and their receptors are broadly expressed in different tissues and are involved in diverse biologic processes. Gene inactivation studies have shown that both stromal cell derived factor-1 (SDF-1) and chemokine receptor 4 (CXCR4) are essential for B lymphopoiesis. However, it is not yet clear by which mechanisms B lymphopoiesis is affected. In the present study, we have examined CXCR4 expression and function on primary B cells representing sequential stages of development (eg, pro-B, pre-B, immature, and mature B cells) in fetal and adult bone marrow. The expression of CXCR4 was observed to be sinusoidal. Expression was highest on pre-B cells, decreased as cells developed into immature B cells, and then increased again upon transition to the mature B-cell stage. The corresponding ligand SDF-1 was shown to trigger vigorous cell signaling and migration responses, which are restricted to early lineage B cells. The responsiveness to SDF-1 was markedly decreased for immature and mature B cells despite relatively high levels of CXCR4 expression. Thus, the diminished responsiveness to SDF-1 by more mature B cells was determined to be disproportionate to the level of CXCR4 expression. These findings raise the possibility that CXCR4 function is differentially controlled during B lymphopoiesis and may be relevant to the compartmentalization of B-cell precursors in the bone marrow.

scholarly journals Mad3 Negatively Regulates B Cell Differentiation in the Spleen by Inducing Id2 Expression

2010 ◽  
Vol 21 (11) ◽  
pp. 1864-1871 ◽  
Author(s):  
Yael Gore ◽  
Frida Lantner ◽  
Gili Hart ◽  
Idit Shachar
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Negative Regulator ◽  
Maturation Process ◽  
B Cell Differentiation ◽  
Final Maturation ◽  
Immature B Cells

Immature B cells migrate to the spleen where they differentiate into mature cells. This final maturation step is crucial to enable B cells to become responsive to antigens and to participate in the immune response. Previously, we showed that Id2 acts as a negative regulator of the differentiation of immature B cells occurring in the spleen. Id2 expression has been found to depend on Myc–Max–Mad transcriptional complexes in mammary epithelial cells. Nearly all studies to date have shown that Mad proteins inhibit proliferation, presumably by antagonizing the function of Myc proteins. In the current study, we followed the Mad family members during peripheral B cell differentiation. We show that Mad3 actively regulates B cell differentiation. Our results demonstrate that high expression levels of Mad3 in immature B cells induce Id2 expression, which inhibits transcription of genes essential for B cell differentiation. During their differentiation to mature cells, B cells reduce their Mad3 expression, enabling the maturation process to occur.

Naive recirculating B cells mature simultaneously in the spleen and bone marrow

Blood ◽  
2006 ◽  
Vol 109 (6) ◽  
pp. 2339-2345 ◽  
Author(s):  
Annaiah Cariappa ◽  
Catharine Chase ◽  
Haoyuan Liu ◽  
Paul Russell ◽  
Shiv Pillai
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Single Pulse ◽  
Lymphoid Organs ◽  
Cell Maturation ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
B Cell Maturation ◽  
Secondary Lymphoid Organs

Abstract We have recently demonstrated that IgDhi B cells can occupy an extravascular perisinusoidal niche in the bone marrow in addition to the well-established follicular niche in conventional secondary lymphoid organs. The spleen has long been considered to be the site at which newly formed B lymphocytes mature into IgDhi naive recirculating B cells, but the existence of mutant mice that have selectively lost mature B cells in the bone marrow prompted an examination of B-cell maturation at this latter site. Following a single pulse of BrdU in intact mice, sequential labeling of more mature B-cell populations in the bone marrow suggested ongoing maturation at this site. Further evidence for B-cell maturation in the bone marrow was obtained from analyses of transitional B cells in splenectomized lymphotoxin α-deficient mice that lack all secondary lymphoid organs. In these mice, antibody-secreting cells recognizing multivalent antigens were also observed in the bone marrow following an intravenous microbial challenge. These data suggest that newly formed B cells mature into IgDhi B cells simultaneously in the spleen and the bone marrow and establish in a stringent manner that humoral immune responses can be initiated in situ in the bone marrow.

scholarly journals Acute Disruption of Bone Marrow B Lymphopoiesis and Apoptosis of Transitional and Marginal Zone B Cells in the Spleen following a Blood-StagePlasmodium chabaudiInfection in Mice

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Viki Bockstal ◽  
Nathalie Geurts ◽  
Stefan Magez
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Marginal Zone ◽  
Parasite Clearance ◽  
B Lymphopoiesis ◽  
Marginal Zone B Cells ◽  
Cell Responses ◽  
Immature B Cells ◽  
Chemokine Cxcl12

B cells and antibodies are essential for the protective immune response against a blood-stagePlasmodiuminfection. Although extensive research has focused on memory as well as plasma B-cell responses during infection, little is known about how malaria affects B-cell development and splenic maturation into marginal zone B (MZB) and follicular B (FoB) cells. In this study, we show that acutePlasmodium chabaudiAS infection in C57Bl/6 mice causes severe disruption of B lymphopoiesis in the bone marrow, affecting in particular pro-, pre-, and immature B cells as well as the expression of the bone marrow B-cell retention chemokine CXCL12. In addition, elevated apoptosis of transitional T2 and marginal zone (MZ) B cells was observed during and subsequent to the control of the first wave of parasitemia. In contrast, Folllicular (Fo) B cells levels were retained in the spleen throughout the infection, suggesting that these are essential for parasite clearance and proper infection control.

Talin1 is required for integrin-dependent B lymphocyte homing to lymph nodes and the bone marrow but not for follicular B-cell maturation in the spleen

Blood ◽  
2010 ◽  
Vol 116 (26) ◽  
pp. 5907-5918 ◽  
Author(s):  
Eugenia Manevich-Mendelson ◽  
Valentin Grabovsky ◽  
Sara W. Feigelson ◽  
Guy Cinamon ◽  
Yael Gore ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
B Lymphocyte ◽  
Ex Vivo ◽  
Cell Maturation ◽  
White Pulp ◽  
Marginal Zone B Cells ◽  
B Cell Maturation

Abstract Talin1 is a key integrin coactivator. We investigated the roles of this cytoskeletal adaptor and its target integrins in B-cell lymphogenesis, differentiation, migration, and function. Using CD19 Cre-mediated depletion of talin1 selectively in B cells, we found that talin1 was not required for B-cell generation in the bone marrow or for the entry of immature B cells to the white pulp of the spleen. Loss of talin1 also did not affect B-cell maturation into follicular B cells but compromised differentiation of marginal zone B cells. Nevertheless, serum IgM and IgG levels remained normal. Ex vivo analysis of talin1-deficient spleen B cells indicated a necessary role for talin1 in LFA-1 and VLA-4 activation stimulated by canonical agonists, but not in B-cell chemotaxis. Consequently, talin1 null B splenocytes could not enter lymph nodes nor return to the bone marrow. Talin1 deficiency in B cells was also impaired in the humoral response to a T cell-dependent antigen. Collectively, these results indicate that talin1 is not required for follicular B-cell maturation in the spleen or homeostatic humoral immunity but is critical for integrin-dependent B lymphocyte emigration to lymph nodes and optimal immunity against T-dependent antigens.

scholarly journals Prolonged survival of B-lineage acute lymphoblastic leukemia cells is accompanied by overexpression of bcl-2 protein

Blood ◽  
1993 ◽  
Vol 81 (4) ◽  
pp. 1025-1031 ◽  
Author(s):  
D Campana ◽  
E Coustan-Smith ◽  
A Manabe ◽  
M Buschle ◽  
SC Raimondi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
B Cells ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Prolonged Survival ◽  
Allogeneic Bone ◽  
Immature B Cells ◽  
B Lineage

Overexpression of bcl-2 delays the onset of apoptosis in lymphohematopoietic cells. We measured levels of bcl-2 protein in normal and leukemic human B-cell progenitors with a specific monoclonal antibody and flow cytometry. Normal immature B cells had low levels of bcl-2 protein; the intensity of fluorescence, expressed as molecules of soluble fluorochrome per cell, within CD10+ cells was 3,460 +/- 1,050 (mean +/- SD; 5 samples). In 16 cases of B-lineage acute lymphoblastic leukemia (ALL), cells had levels of bcl-2 that were strikingly higher than those of their normal counterparts (33,560 +/- 14,570; P < .001 by t-test analysis). We next investigated whether the intensity of bcl-2 expression correlated with the resistance of immature B cells to in vitro culture. In 12 cases of B-lineage ALL, the cells recovered after 7 days of culture on allogeneic bone marrow stromal layers were 69% to 178% (median, 95.5%) of those originally seeded. Prolonged survival of leukemic cells in vitro was observed even in the absence of stromal layers in 6 of these 12 cases; the intensity of bcl-2 protein expression in these cases was 45,000 +/- 13,270, compared with 21,500 +/- 7,260 in the 6 cases in which greater than 99.5% of cells rapidly died by apoptosis under the same culture conditions (P = .003). Five immature B-cell lines, continuously growing in the absence of stroma, had the highest bcl-2 expression (79,400 +/- 20,330). By contrast, most normal CD19+, sIg-immature B cells died despite the presence of bone marrow stromal layers; 9.7% to 28.2% were recovered after 7 days of culture in three experiments. We conclude that abnormal bcl-2 gene expression influences the survival ability of B-cell progenitors. This may contribute to leukemogenesis and explain the aptitude of leukemic lymphoblasts to expand outside the bone marrow microenvironment.

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