scholarly journals A QUANTITATIVE ASSAY FOR THE PROGENITORS OF BONE MARROW-ASSOCIATED LYMPHOCYTES

1972 ◽  
Vol 135 (6) ◽  
pp. 1363-1374 ◽  
Author(s):  
Louis Lafleur ◽  
R. G. Miller ◽  
R. A. Phillips
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Lymphocytes ◽  
Bone Marrow Cells ◽  
Cell Activity ◽  
Kinetic Studies ◽  
Precursor Cells ◽  
Physical Analysis ◽  
Peripheral Lymph ◽  
A Cell

A cell transfer assay system was developed to study the precursors of bone marrow-associated (B) lymphocytes in the adult mouse. The rationale of the assay is to inject into irradiated mice a cell suspension depleted of B lymphocytes, to wait a period of time to let precursor cells differentiate to B lymphocytes, then to correlate the number of B cells present in the recipient mice with the number of precursor cells injected. The assay as described was shown to be linear in the range of 105–3 x 106 fractionated bone marrow cells. Kinetic studies indicated that precursor cells start producing detectable numbers of B cells within 3 days after transplantation; B cell activity then increases with a doubling time of 24 hr. Physical characterization of that precursor cell has shown that it is lighter and sediments faster than small lymphocytes. Precursor cells were found in bone marrow and spleen but could not be detected in peripheral lymph nodes. Results of physical analysis also indicate that the precursors of B lymphocytes described here may not be pluripotent stem cells for the immune system.

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 Evidence for a bone marrow B cell transcribing malignant plasma cell VDJ joined to C mu sequence in immunoglobulin (IgG)- and IgA-secreting multiple myelomas.

1993 ◽  
Vol 178 (3) ◽  
pp. 1091-1096 ◽  
Author(s):  
P Corradini ◽  
M Boccadoro ◽  
C Voena ◽  
A Pileri
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Bone Marrow Cells ◽  
Indirect Evidence ◽  
Specific Marker

Multiple myeloma is a B cell malignancy characterized by the expansion of plasma cells producing monoclonal immunoglobulins (Ig). It has been regarded as a tumor arising at the B, pre-B lymphocyte, or even stem cell level. Precursor cells are presumed to proliferate and differentiate giving rise to the plasma cell clonal expansion. Antigenic features and specific Ig gene rearrangement shared by B lymphocytes and myeloma cells have supported this hypothesis. However, the existence of such a precursor is based upon indirect evidence and is still an open question. During differentiation, B cells rearrange variable (V) regions of Ig heavy chain genes, providing a specific marker of clonality. Using an anchor polymerase chain reaction assay, these rearranged regions from five patients with multiple myeloma were cloned and sequenced. The switch of the Ig constant (C) region was used to define the B cell differentiation stage: V regions are linked to C mu genes in pre-B and B lymphocytes (pre-switch B cells), but to C gamma or C alpha in post-switch B lymphocytes and plasma cells (post-switch B cells). Analysis of bone marrow cells at diagnosis revealed the presence of pre-switch B cells bearing plasma cell V regions still joined to the C mu gene. These cells were not identified in peripheral blood, where tumor post-switch B cells were detected. These pre-switch B cells may be regarded as potential myeloma cell precursors.

scholarly journals Enhanced production of B lymphocytes after castration

Blood ◽  
1995 ◽  
Vol 85 (6) ◽  
pp. 1535-1539 ◽  
Author(s):  
CA Wilson ◽  
SA Mrose ◽  
DW Thomas
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Lymphocytes ◽  
Cellular Immunity ◽  
Bone Marrow Cells ◽  
B Lymphopoiesis ◽  
Male Mice ◽  
Spleen Cells ◽  
Enhanced Production ◽  
Threefold Increase

Castration has long been recognized to stimulate thymic growth and augment cellular immunity. We sought to determine whether castration affects B lymphopoiesis by analyzing the phenotype of bone marrow and spleen cells from animals postcastration. In this report, we show that the bone marrow cells from castrated male mice show a sustained, twofold to threefold increase in numbers of B220+/IgM- cells and of newly formed B220+/IgM+ B cells. Most of the expanded B220+/IgM- cell population consisted of small, HSAhi, CD43- cells characteristic of pre- B cells. The castrated animals also showed increased numbers of splenic B cells, primarily consisting of small IgM+, IgDlo, B220lo, HSAhi cells. Taken together, these results show that castration causes dramatic, long-lived enhancement of B lymphopoiesis in bone marrow and increased numbers of mature B cells in the periphery.

scholarly journals ROLES OF T AND B LYMPHOCYTES IN THE TERMINATION OF UNRESPONSIVENESS TO AUTOLOGOUS THYROGLOBULIN IN MICE

1974 ◽  
Vol 139 (3) ◽  
pp. 643-660 ◽  
Author(s):  
James A. Clagett ◽  
William O. Weigle
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
B Cells ◽  
B Lymphocytes ◽  
Bone Marrow Cells ◽  
Antigen Binding ◽  
Binding Studies ◽  
Normal Complement ◽  
Self Antigen

The data presented in this paper support the hypothesis that unresponsiveness to autologous thyroglobulin (Tg) exists in the T cells and responsiveness exists in the B cells. Such a conclusion is based on the results of antigen-binding studies where few, if any, thymocytes recognized syngeneic Tg. Comparable numbers of antigen-binding lymphocytes for syngeneic Tg were found in the spleens of normal intact mice and of nude mice. The latter fact suggested that B cells exist which recognize self-constituents. From antigen-suicide experiments, a clearer picture of the susceptibility of B cells to iodinated self-antigen and of the obligatory role of antibody in the induction of lesions was developed. Only bone marrow cells (B cells) were affected by [125I]syngeneic Tg, in which case the incidence of lesions was diminished. From adoptive transfer experiments, the results demonstrate that unresponsiveness may be terminated by immunization with a mixture of heterologous (cross-reacting) Tg's. In this situation T cells are required since a B-cell reconstituted host failed to make antibody (plaque-forming cells) and to develop lesions. T cells in this form of an unresponsive state may recognize determinants on the heterologous Tg unrelated to autologous Tg and as such stimulate the normal complement of B cells to produce antibody that both reacts with autologous and heterologous Tg.

scholarly journals Role of variable region gene expression and environmental selection in determining the antiphosphorylcholine B cell repertoire.

1983 ◽  
Vol 158 (6) ◽  
pp. 1948-1961 ◽  
Author(s):  
N R Klinman ◽  
M R Stone
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
Variable Region ◽  
Precursor Cells ◽  
Cell Repertoire ◽  
Region Gene ◽  
B Cell Repertoire

To evaluate the role of environmental selective processes, as opposed to variable region gene expression, in the determination of B cell repertoire expression, we have assessed the phosphorylcholine (PC)-specific repertoire of precursor cells that remain in bone marrow cell populations after the removal of surface immunoglobulin (sIg)-bearing cells. Such cells are assumed to represent a stage in B cell maturation before the expression of sIg, and thus at a time when they have not as yet interfaced with environmental influences that operate through sIg receptors such as antigenic stimulation, tolerance, or antiidiotypic regulation. The repertoire as expressed in these cells, therefore, should reflect the readout of immunoglobulin variable region genes as they are expressed in progenitors to B cells. The results of these studies indicate that, as in mature primary B cell pools of BALB/c mice, the majority of PC-responsive sIg- bone marrow cells are of the T15 clonotype. Thus, environmental selective mechanisms would not appear to be required for the high frequency of B cells of the T15 idiotype in the primary B cell repertoire of BALB/c mice. Analysis of the sIg- bone marrow cells in (CBA/N X BALB/c)F1 male mice demonstrated that the deficit of PC-responsive mature B cells, which is a characteristic of this murine strain, must occur after receptor expression, since a normal frequency of PC-responsive and T15-expressing cells is present in their sIg- bone marrow population. Finally, these same mice were used to obtain bone marrow cell preparations from individual leg bones, so as to permit an analysis of the occurrence of T15+ and T15- clonotypes within individual bone marrow populations. The findings from these studies indicate that T15+ B cells occur as a high frequency event within bone marrow generative cell pools. Furthermore, bone marrow populations that are positive for PC-responsive precursor cells often display multiple copies of such precursor cells that are exclusively either T15+ or T15-. This finding indicates that clonal expansion of cells within the B cell lineage apparently occurs before immunoglobulin receptor acquisition.

scholarly journals INDUCTION OF A HEMOLYSIN RESPONSE IN VITRO

1971 ◽  
Vol 133 (6) ◽  
pp. 1325-1333 ◽  
Author(s):  
Klaus-Ulrich Hartmann
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
B Cells ◽  
Close Contact ◽  
Precursor Cells ◽  
Spleen Cells ◽  
High Concentrations ◽  
Thymus Cells ◽  
Bone Marrow Chimeras

Spleen cells of bone marrow chimeras (B cells) and of irradiated mice injected with thymus cells and heterologous erythrocytes (educated T cells) were mixed and cultured together (17). The number of PFC developing in these cultures was dependent both on the concentration of the B cells and of the educated T cells. In excess of T cells the number of developing PFC is linearly dependent on the number of B cells. At high concentrations of T cells more PFC developed; the increase in the number of PFC was greatest between the 3rd and 4th day of culture. Increased numbers of educated T cells also assisted the development of PFC directed against the erythrocytes. It is concluded that the T cells not only play a role during the triggering of the precursor cells but also during the time of proliferation of the B cells; close contact between B and T cells seems to be needed to allow the positive activity of the T cells.

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.

scholarly journals Normal cycling patterns of hematopoietic stem cell subpopulations: an assay using long-term in vivo BrdU infusion

Blood ◽  
1985 ◽  
Vol 66 (6) ◽  
pp. 1460-1462 ◽  
Author(s):  
ME Pietrzyk ◽  
GV Priestley ◽  
NS Wolf
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Improved Method ◽  
Hematopoietic Stem ◽  
Infusion Study ◽  
A Cell ◽  
Cell Subpopulations ◽  
Over Time

It was found in a long-term bromodeoxyuridine (BrdU) infusion study that two or more different subpopulations of bone marrow stem cells exist in mice. One of these subpopulations appears to be noncycling and forms approximately 10% of eight-day CFU-S. Another one, a subpopulation of slowly cycling bone marrow cells, is represented as 14- day CFU-S. The 14-day CFU-S have a regular increment in the percentage of the subpopulation entering the cycle over time, with a cell generation half-time of 21 days. The cycling status in these experiments was ascertained by in vivo continuous long-term BrdU infusion. An improved method is presented for long-term BrdU infusion with UV killing of cycled cells.

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