scholarly journals MATURATION OF B LYMPHOCYTES IN THE RAT

1973 ◽  
Vol 138 (6) ◽  
pp. 1331-1344 ◽  
Author(s):  
Samuel Strober ◽  
Jeanette Dilley
Keyword(s):  
B Cells ◽  
B Lymphocytes ◽  
Thoracic Duct ◽  
Time Course ◽  
Turnover Rate ◽  
Bone Marrow Cells ◽  
Thoracic Duct Lymph ◽  
Duct Cells ◽  
Turn Over ◽  
Marrow Cells

The migration pattern, tissue distribution, and turnover rate of unprimed and primed B lymphocytes involved in the adoptive anti-DNP response was studied. The adoptive primary response restored by unprimed spleen or thoracic duct cells passaged through an intermediate host (intravenous injection and subsequent collection in the thoracic duct lymph) was markedly diminished as compared with that restored by unpassaged cells. On the other hand, the adoptive response restored by passaged spleen or thoracic duct cells from DNP-primed donors was greater than or the same as that restored with unpassaged cells, respectively. This suggests that unprimed B cells change from nonrecirculating to recirculating lymphocytes after exposure to antigen. Studies of the adoptive anti-DNP response restored by unprimed or primed bone marrow cells showed little change in the time-course or amplitude of the response restored by either population of cells. The relative inability of marrow cells to carry immunological memory was related to the inability of recirculating memory cells to penetrate the marrow. The turnover rate of unprimed and primed B cells was investigated by treating the cell donors with [3H]thymidine for 48 h before removal of thoracic duct or spleen cells. The adoptive anti-DNP response restored by unprimed or primed cells was not affected by [3H]thymidine treatment. This indicates that both populations of cells turn over slowly. However, our previous studies show that unprimed B cells involved in the adoptive antibody response to ferritin turn over rapidly. The different findings are discussed in the context of antigen-dependent B-cell maturation.

scholarly journals THE LIFE-SPAN AND RECIRCULATION OF MARROW-DERIVED SMALL LYMPHOCYTES FROM THE RAT THORACIC DUCT

1972 ◽  
Vol 135 (2) ◽  
pp. 185-199 ◽  
Author(s):  
Jonathan C. Howard
Keyword(s):  
Bone Marrow ◽  
Life Span ◽  
B Lymphocytes ◽  
Thoracic Duct ◽  
Bone Marrow Cells ◽  
Thoracic Duct Lymph ◽  
Clear Cut ◽  
Duct Lymph ◽  
Order Of Magnitude ◽  
Marrow Cells

These experiments describe the preparation of pure marrow-derived lymphocyte suspensions from the thoracic duct of thymectomized, irradiated rats reconstituted with bone marrow cells. The majority of marrow-derived cells were small lymphocytes morphologically indistinguishable from small lymphocytes in thoracic duct lymph of normal donors. Marrow-derived small lymphocytes (B lymphocytes) were a predominantly long-lived population; the frequency of short-lived B lymphocytes in the thoracic duct was not significantly higher than the frequency of short-lived small lymphocytes in normal lymph. B lymphocytes transferred to normal recipients recirculated from blood to lymph. The first appearance of intravenously injected B lymphocytes in the thoracic duct was delayed relative to lymphocytes from normal donors and there was no clear cut modal recirculation time. Nevertheless their recirculation over a 48 hr period after transfusion was of the same order of magnitude as that of lymphocytes from normal donors.

scholarly journals Prolonged survival in vivo of unprimed B cells responsive to a T-independent antigen.

1985 ◽  
Vol 161 (6) ◽  
pp. 1581-1586 ◽  
Author(s):  
Y Ron ◽  
J Sprent
Keyword(s):  
Lymph Node ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Thoracic Duct ◽  
Thoracic Duct Lymph ◽  
Cell Transfer ◽  
Adult Mice ◽  
Duct Lymph

Despite earlier evidence to the contrary, it has recently been claimed that most B lymphocytes, including lymph node (LN) and thoracic duct B cells, are short-lived cells of recent marrow origin. To seek direct information on this question, we transferred unprimed LN or thoracic duct B cells from normal mice to xid mice, i.e., mice unresponsive to the T-independent antigen, trinitrophenyl (TNP)-Ficoll. At varying periods after B cell transfer the recipients were challenged with TNP-Ficoll; anti-TNP plaque-forming cells were assayed in the spleen 6 d later. The results showed that the B cell recipients retained responsiveness to TNP-Ficoll for at least 3 mo after transfer. Responsiveness increased within the first 3 wk but then remained relatively constant. These findings imply that, at least for TNP-Ficoll-reactive cells, B cells residing in LN and thoracic duct lymph are not short-lived cells of recent marrow. Indeed, the data suggest that once the pool of recirculating B cells is fully formed in adult mice, further input of newly formed cells from the marrow into the recirculating pool is very limited.

scholarly journals CELL TO CELL INTERACTION IN THE IMMUNE RESPONSE

1968 ◽  
Vol 128 (4) ◽  
pp. 801-820 ◽  
Author(s):  
J. F. A. P. Miller ◽  
G. F. Mitchell
Keyword(s):  
Thoracic Duct ◽  
Bone Marrow Cells ◽  
Cell Types ◽  
Cell Interaction ◽  
Thoracic Duct Lymph ◽  
Spleen Cells ◽  
Sheep Erythrocytes ◽  
Duct Cells ◽  
Duct Lymph ◽  
Thymectomized Mice

An injection of viable thymus or thoracic duct lymphocytes was absolutely essential to enable a normal or near-normal 19S liemolysin-forming cell response in the spleens of neonatally thymectomized mice challenged with sheep erythrocytes. Syngeneic thymus lymphocytes were as effective as thoracic duct lymphocytes in this system and allogeneic or semiallogeneic cells could also reconstitute their hosts. No significant elevation of the response was achieved by giving either bone marrow cells, irradiated thymus or thoracic duct cells, thymus extracts or yeast. Spleen cells from reconstituted mice were exposed to anti-H2 sera directed against either the donor of the thymus or thoracic duct cells, or against the neonatally thymectomized host. Only isoantisera directed against the host could significantly reduce the number of hemolysin-forming cells present in the spleen cell suspensions. It is concluded that these antibody-forming cells are derived, not from the inoculated thymus or thoracic duct lymphocytes, but from the host. Thoracic duct cells from donors specifically immunologically tolerant of sheep erythrocytes had a markedly reduced restorative capacity in neonatally thymectomized recipients challenged with sheep erythrocytes. These results have suggested that there are cell types, in thymus or thoracic duct lymph, with capacities to react specifically with antigen and to induce the differentiation, to antibody-forming cells, of hemolysin-forming cell precursors derived from a separate cell line present in the neonatally thymectomized hosts.

scholarly journals Defective lymphopoiesis in bone marrow of motheaten (me/me) and viable motheaten (mev/mev) mutant mice. I. Analysis of development of prothymocytes, early B lineage cells, and terminal deoxynucleotidyl transferase-positive cells.

1986 ◽  
Vol 164 (4) ◽  
pp. 1129-1144 ◽  
Author(s):  
D L Greiner ◽  
I Goldschneider ◽  
K L Komschlies ◽  
E S Medlock ◽  
F J Bollum ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Lymphocytes ◽  
Bone Marrow Cells ◽  
Precursor Cells ◽  
T And B Lymphocytes ◽  
Normal Numbers ◽  
B Lineage ◽  
Marrow Cells ◽  
B Lineage Cells

This study identifies defects in the early stages of lymphopoiesis that may contribute to the abnormalities in the development and/or function of peripheral T and B lymphocytes in mice homozygous for the motheaten (me/me) and viable motheaten (mev/mev) mutations. The results indicate that in me/me and mev/mev mice prothymocytes in bone marrow are present in essentially normal numbers, as determined by intrathymic injection, but apparently lack the ability to home effectively to the thymus, as determined by intravenous transfer; early B lineage cells in bone marrow, identified by the B220 antigen, are markedly depleted, including immature B cells (sIg+), pre-B cells (cIg+, sIg-), and pro-B cells (B220+, cIg-, sIg-); TdT+ bone marrow cells, especially a subset that expresses the B220 B lineage antigen, are markedly depleted by two weeks of age; normal numbers of TdT+ thymocytes are present during the first 3 wk of postnatal life, but rapidly decrease thereafter. The results further indicate that neither the defective thymus homing capacity of prothymocytes nor the deficiency of TdT+ bone marrow cells is due to autoantibodies. The possible relationship of the defective development of lymphoid precursor cells to the premature onset of thymic involution and to the abnormalities of peripheral T and B lymphocytes in me/me and mev/mev mice is discussed; as are the results of in vitro studies (presented in a companion paper), which suggest that a primary defect in the stromal microenvironment of the bone marrow is responsible for the abnormal development of the lymphoid precursor cells.

scholarly journals CELL TO CELL INTERACTION IN THE IMMUNE RESPONSE

1968 ◽  
Vol 128 (4) ◽  
pp. 839-853 ◽  
Author(s):  
G. J. V. Nossal ◽  
A. Cunningham ◽  
G. F. Mitchell ◽  
J. F. A. P. Miller
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Immune Responses ◽  
Thoracic Duct ◽  
Bone Marrow Cells ◽  
Cell Interaction ◽  
Thoracic Duct Lymph ◽  
Chromosomal Marker ◽  
Sheep Erythrocytes ◽  
Marrow Cells

Two new methods are described for making chromosomal spreads of single antibody-forming cells. The first depends on the controlled rupture of cells in small microdroplets through the use of a mild detergent and application of a mechanical stress on the cell. The second is a microadaptation of the conventional Ford technique. Both methods have a success rate of over 50%, though the quality of chromosomal spreads obtained is generally not as good as with conventional methods. These techniques have been applied to an analysis of cell to cell interaction in adoptive immune responses, using the full syngeneic transfer system provided by the use of CBA and CBA/T6T6 donor-recipient combinations. When neonatally thymectomized mice were restored to adequate immune responsiveness to sheep erythrocytes by injections of either thymus cells or thoracic duct lymphocytes, it was shown that all the actual dividing antibody-forming cells were not of donor but of host origin. When lethally irradiated mice were injected with chromosomally marked but syngeneic mixtures of thymus and bone marrow cells, a rather feeble adoptive immune response ensued; all the antibody-forming cells identified were of bone marrow origin. When mixtures of bone marrow cells and thoracic duct lymphocytes were used, immune restoration was much more effective, and over three-quarters of the antibody-forming mitotic figures carried the bone marrow donor chromosomal marker. The results were deemed to be consistent with the conclusions derived in the previous paper of this series, namely that thymus contains some, but a small number only of antigen-reactive cells (ARC), bone marrow contains antibody-forming cell precursors (AFCP) but no ARC, and thoracic duct lymph contains both ARC and AFCP with a probable predominance of the former. A vigorous immune response to sheep erythrocytes probably requires a collaboration between the two cell lineages, involving proliferation first of the ARC and then of the AFCP. The results stressed that the use of large numbers of pure thoracic duct lymphocytes in adoptive transfer work could lead to good adoptive immune responses, but that such results should not be construed as evidence against cell collaboration hypotheses. Some possible further uses of single cell chromosome techniques were briefly discussed.

scholarly journals INITIATION OF ANTIBODY RESPONSES BY DIFFERENT CLASSES OF LYMPHOCYTES

1972 ◽  
Vol 136 (4) ◽  
pp. 851-871 ◽  
Author(s):  
Samuel Strober
Keyword(s):  
B Cells ◽  
Antibody Response ◽  
Thoracic Duct ◽  
Primary Response ◽  
Thoracic Duct Lymph ◽  
Secondary Antibody ◽  
Duct Cells ◽  
Precursor B Cells ◽  
B1 Cells ◽  
Horse Spleen Ferritin

The life-span and migratory characteristics of rat thoracic duct cells which initiate the adoptive primary and secondary antibody response to diphtheria toxoid (DT) and horse spleen ferritin (HSF) were investigated. The experimental results show that thoracic duct lymphocytes from normal (unimmunized) donors are able to restore the adoptive response of irradiated hosts to HSF. Thoracic duct cells passaged through an intermediate host (intravenous injection and subsequent collection in the thoracic duct lymph) showed a marked reduction in their restorative action as compared with unpassaged cells. In addition, the restorative action of cells from donors treated with thymidine-3H for 48 hr before cannulation of the thoracic duct was markedly decreased. This indicates that a population of lymphocytes involved in the adoptive primary response is unable to recirculate from the blood to the lymph and is turning over rapidly (short lived). The nonrecirculating, short-lived lymphocytes are proably "B" cells, since a combination of spleen cells from neonatally thymectomized rats and passaged or thymidine-3H-treated cells restores a vigorous response to HSF. On the other hand, passaged or thymidine-3H-treated thoracic duct cells from donors immunized to DT or HSF are able to restore a vigorous adoptive secondary antibody response. Experiments with the hapten-protein conjugate, DNP-DT, show that the majority of both helper ("T") and precursor ("B") cells are able to recirculate and are slowly turning over (long lived). The findings suggest that T lymphocytes involved in both the primary and secondary antibody response are recirculating, long-lived cells. However, B lymphocytes involved in the primary response are nonrecirculating, short-lived cells ("B1" cells) which undergo a fundamental physiological change to recirculating, long-lived cells ("B2" cells) involved in the secondary antibody response.

Transformation of murine bone marrow cells with combined v-raf-v-myc oncogenes yields clonally related mature B cells and macrophages

1990 ◽  
Vol 10 (7) ◽  
pp. 3562-3568
Author(s):  
M Principato ◽  
J L Cleveland ◽  
U R Rapp ◽  
K L Holmes ◽  
J H Pierce ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Cell Lines ◽  
Bone Marrow Cells ◽  
Hematopoietic Differentiation ◽  
Developmental Relationships ◽  
Murine Bone Marrow ◽  
B Lineage ◽  
Marrow Cells

Murine bone marrow cells infected with replication-defective retroviruses containing v-raf alone or v-myc alone yielded transformed pre-B cell lines, while a retroviral construct containing both v-raf and v-myc oncogenes produced clonally related populations of mature B cells and mature macrophages. The genealogy of these transformants demonstrates that mature myeloid cells were derived from cells with apparent B-lineage commitment and functional immunoglobulin rearrangements. This system should facilitate studies of developmental relationships in hematopoietic differentiation and analysis of lineage determination.

Mesenchymal Stromal Cells Enhance G-CSF-Induced Mobilization Of Hematopoietic Stem- and Progenitor Cells

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2460-2460
Author(s):  
Evert-Jan F. M. de Kruijf ◽  
Ingmar van Hengel ◽  
Jorge M Perez-Galarza ◽  
Willem E. Fibbe ◽  
Melissa van Pel
Keyword(s):  
Bone Marrow ◽  
B Lymphocytes ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Peripheral Blood ◽  
Bone Marrow Cells ◽  
Calf Serum ◽  
Intraperitoneal Administration ◽  
Hematopoietic Stem ◽  
Marrow Cells

Abstract Hematopoietic stem- and progenitor cell (HSPC) mobilization is a property of most hematopoietic growth factors, such as Granulocyte Colony Stimulating Factor (G-CSF). Not all donors mobilize equally well and therefore the number of HSPC that are obtained following mobilization may be limited. Mesenchymal stromal cells (MSC) have the capacity to differentiate into cells of the mesodermal lineage and have immunomodulatory properties in vivo and in vitro. Here, we have investigated the effect of MSC co-administration on G-CSF-induced HSPC mobilization. MSC were obtained from bone marrow cells (bone marrow-derived) or bone fragments (bone-derived) and were expanded in alpha-MEM containing 10% fetal calf serum until sufficient cell numbers were obtained. Bone marrow or bone-derived MSC were administered intravenously for three days at a dose of 200 x103 cells per day to male C57BL/6 recipients that were simultaneously mobilized with G-CSF (10 μg per day intraperitoneally for 3 days) or PBS as a control. Co-injection of G-CSF and MSC lead to a 2-fold increase in HSPC mobilization compared to G-CSF alone (8,563 ± 3,309 vs. 4,268 ± 1,314 CFU-C per ml peripheral blood respectively; n=13, p<0.01). Administration of MSC alone did not induce HSPC mobilization (273 ± 229 CFU-C/ml blood; n=13). Furthermore, co-injection of splenocytes and G-CSF did not enhance HSPC mobilization, showing that the administration of exogeneous cells as such is not sufficient for enhancement of HSPC mobilization. It has been reported that G-CSF-induced HSPC mobilization is associated with a decrease in the number of osteal macrophages, B lymphocytes and erythroid progenitors. Administration of MSC alone induced a significant decrease in the frequency of osteal macrophages (7.9 ± 1.2 vs 6.2 ± 1.4% bone marrow cells for PBS vs. MSC respectively; n=8, p<0.05), but did not affect osteoblast numbers. Furthermore, the frequency of B lymphocytes was significantly decreased following MSC administration (29.9 ± 4.0 vs. 16.5 ± 4.9% bone marrow cells for PBS vs. MSC respectively; n=13, p<0.0001). No differences were observed in erythroid numbers following MSC administration. To investigate the mechanisms underlying these observations, the migratory capacity of luciferase transduced MSC was studied through bioluminescence imaging. Following intravenous injection, MSC were detected in the lungs, but not in other organs. In addition, no difference in MSC migration was observed between G-CSF and PBS treated mice. Moreover, intraperitoneal administration of G-CSF and MSC resulted in increased HSPC mobilization compared to G-CSF alone (10,178 ±3,039 vs. 5,158 ± 2,436 CFU-C per ml peripheral blood; n=5-12). Together, these data point to an endocrine effect of MSC on G-CSF-induced HSPC mobilization. No differences in IL-6, CXCL-12 or M-CSF levels in bone marrow extracellular fluid were observed. In conclusion, G-CSF-induced HSPC mobilization is enhanced by injection of MSC. We hypothesize that the MSC-induced partial depletion of B lymphocytes and osteal macrophages in the bone marrow are crucial factors involved in the enhancement of G-CSF-induced HSPC mobilization. Disclosures: No relevant conflicts of interest to declare.

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