scholarly journals Precursors of murine B lymphocytes. Physical and functional characterization, and distinctions from myeloid stem cells.

1981 ◽  
Vol 153 (1) ◽  
pp. 154-165 ◽  
Author(s):  
C J Paige ◽  
P W Kincade ◽  
L A Shinefeld ◽  
V L Sato

The emergence of functional B cells was monitored in irradiated or unirradiated CBA/N recipients of either adult bone marrow or fetal liver from CBA/HT6T6 donors. The cells that are primarily responsible for the generation of B lymphocytes, at least during the first 6 wk, are rapidly sedimenting (4.5-6 mm/h), lack surface immunoglobulin, and are found in both the adult bone marrow and the fetal liver from day 12 onward. These pre-B cells are distinct from the colony-forming unit spleen (CFU-s) as demonstrated by the following criteria: (a) absence from yolk sac (19), (b) lack of correlation between CFU-s number and the ability to generate B cells in fetal liver populations of different ages of gestation, and (c) hybridoma antibodies that significantly inhibited B cell reconstitution but have no effect on CFU-s numbers. The antigen detected by this antiserum is present on both the fetal liver and bone marrow B cell progenitor, although its expression is not restricted to the B lineage. The pre-B cells that we monitor are not homogeneous, however, as both physical and functional differences are found. These observations reinforce our thesis that committed progenitor cells for the humoral immune system are formed early in development and thereafter constitute the major precursor pool for the generation of B lymphocytes.

1977 ◽  
Vol 145 (5) ◽  
pp. 1382-1386 ◽  
Author(s):  
E S Metcalf ◽  
N H Sigal ◽  
N R Klinman

The susceptibility to in vitro tolerance induction has been implicated as a characteristic of B cells early in their development, since DNP-reactive B cells are tolerizable only during the first days after birth, and 25% of adult bone marrow cells are tolerizable. In the present study, a modification of the in vitro splenic focus technique was utilized to determine if PC-specific B cells, by virtue of their late expression (approximately 1 wk post-parturition), also display susceptibility to tolerance induction. The results demonstrate that at 7-10 days after birth, when over 90% of the DNP-specific splenic B cells are resistant to tolerance induction, the majority of PC-specific B cells are tolerizable. These results re-emphasize tolerance susceptibility as a characteristic of developing clones, confirm the late acquisition of PC-specific B cells, and support the contention that the acquisition of the specificity repertoire is a highly ordered, specifically predetermined process which is independent of antigen-driven events.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yi Yu ◽  
Alejandra Vargas Valderrama ◽  
Zhongchao Han ◽  
Georges Uzan ◽  
Sina Naserian ◽  
...  

Abstract Background Mesenchymal stem cells (MSCs) exhibit active abilities to suppress or modulate deleterious immune responses by various molecular mechanisms. These cells are the subject of major translational efforts as cellular therapies for immune-related diseases and transplantations. Plenty of preclinical studies and clinical trials employing MSCs have shown promising safety and efficacy outcomes and also shed light on the modifications in the frequency and function of regulatory T cells (T regs). Nevertheless, the mechanisms underlying these observations are not well known. Direct cell contact, soluble factor production, and turning antigen-presenting cells into tolerogenic phenotypes, have been proposed to be among possible mechanisms by which MSCs produce an immunomodulatory environment for T reg expansion and activity. We and others demonstrated that adult bone marrow (BM)-MSCs suppress adaptive immune responses directly by inhibiting the proliferation of CD4+ helper and CD8+ cytotoxic T cells but also indirectly through the induction of T regs. In parallel, we demonstrated that fetal liver (FL)-MSCs demonstrates much longer-lasting immunomodulatory properties compared to BM-MSCs, by inhibiting directly the proliferation and activation of CD4+ and CD8+ T cells. Therefore, we investigated if FL-MSCs exert their strong immunosuppressive effect also indirectly through induction of T regs. Methods MSCs were obtained from FL and adult BM and characterized according to their surface antigen expression, their multilineage differentiation, and their proliferation potential. Using different in vitro combinations, we performed co-cultures of FL- or BM-MSCs and murine CD3+CD25−T cells to investigate immunosuppressive effects of MSCs on T cells and to quantify their capacity to induce functional T regs. Results We demonstrated that although both types of MSC display similar cell surface phenotypic profile and differentiation capacity, FL-MSCs have significantly higher proliferative capacity and ability to suppress both CD4+ and CD8+ murine T cell proliferation and to modulate them towards less active phenotypes than adult BM-MSCs. Moreover, their substantial suppressive effect was associated with an outstanding increase of functional CD4+CD25+Foxp3+ T regs compared to BM-MSCs. Conclusions These results highlight the immunosuppressive activity of FL-MSCs on T cells and show for the first time that one of the main immunoregulatory mechanisms of FL-MSCs passes through active and functional T reg induction.


1997 ◽  
Vol 177 (1) ◽  
pp. 18-25 ◽  
Author(s):  
Yoshihiro Watanabe ◽  
Yuichi Aiba ◽  
Yoshimoto Katsura

Author(s):  
Daniel E Eldridge ◽  
Charlie C Hsu

Murine norovirus (MNV), which can be used as a model system to study human noroviruses, can infect macrophages/monocytes, neutrophils, dendritic, intestinal epithelial, T and B cells, and is highly prevalent in laboratory mice. We previouslyshowed that MNV infection significantly reduces bone marrow B cell populations in a Stat1-dependent manner. We show here that while MNV-infected Stat1−/− mice have significant losses of bone marrow B cells, splenic B cells capable of mounting an antibody response to novel antigens retain the ability to expand. We also investigated whether increased granulopoiesis after MNV infection was causing B cell loss. We found that administration of anti-G-CSF antibody inhibits the pronounced bone marrow granulopoiesis induced by MNV infection of Stat1−/− mice, but this inhibition did not rescue bone marrow B cell losses. Therefore, MNV-infected Stat1−/− mice can still mount a robust humoral immune response despite decreased bone marrow B cells. This suggests that further investigation will be needed to identify other indirect factors or mechanisms that are responsible for the bone marrow B cell losses seen after MNV infection. In addition, this work contributes to our understanding of the potential physiologic effects of Stat1-related disruptions in research mouse colonies that may be endemically infected with MNV.


1989 ◽  
Vol 1 (1) ◽  
pp. 27-35 ◽  
Author(s):  
R D Sanderson ◽  
P Lalor ◽  
M Bernfield

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.


1976 ◽  
Vol 144 (2) ◽  
pp. 494-506 ◽  
Author(s):  
I Scher ◽  
S O Sharrow ◽  
R Wistar ◽  
R Asofsky ◽  
W E Paul

The density of total Ig and of IgM, IgG1, IgG2, and IgA on the surface of adult murine splenic B lymphocytes was measured using the technique of rapid flow microfluorometry. In addition, the density of total surface Ig and of IgM on B lymphocytes derived from adult bone marrow, lymph nodes, and Peyer's patches, and from neonatal spleen was determined. Adult spleen and lymph node B lymphocytes are characterized by the presence of a large population of cells with a low-to-intermediate density of total surface Ig, which is seen as a peak in the fluorescence profiles when these cells are labeled with fluorescein-conjugated (F1) anti-Ig. This peak is not detected when neonatal spleen or adult bone marrow are examined; the development of this peak among spleen cells occurs during the first 4 wk of life. Although the characteristic fluorescence intensity peak is not seen when adult spleen cells are labeled with Fl anti-mu, changes in the density of surface IgM do occur during the first few weeks of life and are detected as a decrease in the frequency of cells which have relatively large amounts of surface IgM. The differences seen in the fluorescence patterns of adult spleen cells labeled with Fl anti-Ig and Fl anti-mu may be due to the appearance of IgD on the surface of mature splenic B lymphocytes. This is supported by the similarity of the fluorescence profiles of adult bone marrow cells stained with Fl anti-Ig and Fl anti-mu, as the latter population of cells is reported to lack surface IgD.


1986 ◽  
Vol 6 (4) ◽  
pp. 1108-1116 ◽  
Author(s):  
M Yagi ◽  
R Gelinas ◽  
J T Elder ◽  
M Peretz ◽  
T Papayannopoulou ◽  
...  

The human alpha-like globins undergo a switch from the embryonic zeta-chain to the alpha-chain early in human development, at approximately the same time as the beta-like globins switch from the embryonic epsilon-to the fetal gamma-chains. We investigated the chromatin structure of the human alpha-globin gene cluster in fetal and adult erythroid cells. Our results indicate that DNase I-hypersensitive sites exist at the 5' ends of the alpha 1- and alpha 2-globin genes as well as at several other sites in the cluster in all erythroid cells examined. In addition, early and late fetal liver erythroid cells and adult bone marrow cells contain hypersensitive sites at the 5' end of the zeta gene, and in a purified population of 130-day-old fetal erythroid cells, the entire zeta-to alpha-globin region is sensitive to DNase I digestion. The presence of features of active chromatin in the zeta-globin region in fetal liver and adult bone marrow cells led us to investigate the transcription of zeta in these cells. By nuclear runoff transcription studies, we showed that initiated polymerases are present on the zeta-globin gene in these normal erythroid cells. Immunofluorescence with anti-zeta-globin antibodies also showed that late fetal liver cells contain zeta-globin. These findings demonstrate that expression of the embryonic zeta-globin continues at a low level in normal cells beyond the embryonic to fetal globin switch.


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