Lymphokines and monokines as regulators of human lymphoproliferation.

1984 ◽  
Vol 30 (9) ◽  
pp. 1539-1545 ◽  
Author(s):  
N M Kouttab ◽  
S Mehta ◽  
J Morgan ◽  
N Tannir ◽  
C Sahasrabuddhe ◽  
...  
Keyword(s):  
B Lymphocytes ◽  
Biological Fluids ◽  
Interleukin 1 ◽  
Interleukin 2 ◽  
Proliferation And Differentiation ◽  
The Face ◽  
B Cell Growth Factor ◽  
Immunoregulatory Cells ◽  
Immunodeficiency Syndromes

Abstract The development of a competent immunoregulatory response in the face of an antigenic challenge is modulated by soluble proteins of relatively low molecular mass. Lymphokines and monokines, secreted by cells of T lineage and cells of the monocyte/microphage series, respectively, function in a bimodal amplification network that results in the proliferation and differentiation of the immunoregulatory cells. Interleukin 1 is typically assayed by its effect on thymocytes or by its ability to promote the T cell-dependent release of interleukin 2. Interleukin 2 is routinely measured by its ability to support the long-term growth of cultured T cells, whereas B cell growth factor is measured by its ability to support the long-term growth of cultured B lymphocytes. The availability of homogeneous purified factors and the subsequent availability of monoclonal antibodies against these reagents should allow for the development of rapid quantitative assays for these analytes in diverse biological fluids. In addition, large quantities of purified reagents will promote studies to determine therapeutic efficacy in several immunodeficiency syndromes.

scholarly journals Human normal CD5+ B lymphocytes can be induced to differentiate to CD5- B lymphocytes with germinal center cell features

Blood ◽  
1989 ◽  
Vol 73 (5) ◽  
pp. 1259-1263 ◽  
Author(s):  
F Caligaris-Cappio ◽  
M Riva ◽  
L Tesio ◽  
M Schena ◽  
G Gaidano ◽  
...  
Keyword(s):  
Cell Cycle ◽  
B Cells ◽  
B Lymphocytes ◽  
Germinal Center ◽  
Interleukin 2 ◽  
Significant Proportion ◽  
S Phase ◽  
Low Molecular Weight ◽  
B Cell Growth Factor ◽  
Center Cell

Abstract A significant proportion of cord blood CD5+ B cells express the activation molecules CD23, CD25, and transferrin receptor; react with the cell-cycle-associated monoclonal antibody (MoAb) Ki67; can be induced to enter the S phase of cell cycle by interleukin-2 (IL-2), IL- 4, or low-molecular-weight B-cell growth factor (Imw-BCGF) and, exposed to IL-1 and IL-2, acquire the features (sIgD-, CD5-, CD10+, CD38+) of B blasts proliferating in the germinal centers of secondary follicles. These findings indicate that CD5+ B cells are preactivated and, in the proper microenvironment, may give rise to CD5- B cells.

Clinical and immunological and microbiological effectiveness of the use of recombinant interleukin 2 in the complex therapy of bacterial meningitis

2021 ◽  
pp. 11-18
Author(s):  
O.A. Gizinger
Keyword(s):  
Bacterial Meningitis ◽  
B Lymphocytes ◽  
Biological Effects ◽  
Interleukin 2 ◽  
Clonal Proliferation ◽  
Recombinant Cytokine ◽  
Proliferation And Differentiation ◽  
Complex Therapy ◽  
Recombinant Interleukin 2

The article shows the scheme of complex therapy of bacterial meningitis using the recombinant cytokine interleukin 2. The clinical, immunological and microbiological efficacy of the use of recombinant interleukin 2 in the complex therapy of bacterial meningitis is shown. The biological effects of recombinant IL-2 justify its use in the complex therapy of meningitis due to its influence on the activity of metabolic processes at the cellular and subcellular levels, the ability to stabilize the system of lipid peroxidation of cell membranes, to influence the processes of clonal proliferation and differentiation of T- and B-lymphocytes improving the quality of the therapy.

scholarly journals Human normal CD5+ B lymphocytes can be induced to differentiate to CD5- B lymphocytes with germinal center cell features

Blood ◽  
1989 ◽  
Vol 73 (5) ◽  
pp. 1259-1263 ◽  
Author(s):  
F Caligaris-Cappio ◽  
M Riva ◽  
L Tesio ◽  
M Schena ◽  
G Gaidano ◽  
...  
Keyword(s):  
Cell Cycle ◽  
B Cells ◽  
B Lymphocytes ◽  
Germinal Center ◽  
Interleukin 2 ◽  
Significant Proportion ◽  
S Phase ◽  
Low Molecular Weight ◽  
B Cell Growth Factor ◽  
Center Cell

A significant proportion of cord blood CD5+ B cells express the activation molecules CD23, CD25, and transferrin receptor; react with the cell-cycle-associated monoclonal antibody (MoAb) Ki67; can be induced to enter the S phase of cell cycle by interleukin-2 (IL-2), IL- 4, or low-molecular-weight B-cell growth factor (Imw-BCGF) and, exposed to IL-1 and IL-2, acquire the features (sIgD-, CD5-, CD10+, CD38+) of B blasts proliferating in the germinal centers of secondary follicles. These findings indicate that CD5+ B cells are preactivated and, in the proper microenvironment, may give rise to CD5- B cells.

Platelet Activating Factor Inhibits Both the Proliferation and the Differentiation of Activated B Lymphocytes in Response to Interleukin-2

1992 ◽  
Vol 5 (3) ◽  
pp. 155-163 ◽  
Author(s):  
B. Dugas ◽  
J.P. Kolb ◽  
Nathalie Paul-Eugene ◽  
J.M. Mencia-Huerta ◽  
P. Braquet
Keyword(s):  
B Lymphocytes ◽  
B Lymphocyte ◽  
Interleukin 2 ◽  
Platelet Activating Factor ◽  
Interleukin 4 ◽  
Delayed Response ◽  
Suppression Effect ◽  
Paf Antagonists ◽  
Proliferation And Differentiation ◽  
Humoral Responses

The role of the platelet activating factor in human B lymphocyte responses to Interleukin-2 was examined and compared with that of Interleukin-4 by assessing the ability of this molecule to modulate proliferation and differentiation. Highly purified B lymphocytes were prestimulated for 48 h with Staphylococcus aureus Cowan Strain I and then were cultured with Interleukin-2 alone or in combination with either Interleukin-4 or the platelet activating factor and the proliferation (after 3 days) and the immunoglobulins (IgG and IgM) production (after 7 days) were evaluated. When SAC-activated B lymphocytes were preincubated overnight with PAF (0.0001 to 1 μM) or with IL-4 (1 to 100 U/ml) both the IL-2-induced proliferation and immunoglobulins secretion were inhibited. This inhibition was not a reflection of a decreased expression of the IL-2 receptor (CD25) because this expression was not modified on SAC-activated B lymphocytes after preincubation with either PAF or IL-4. Moreover, this suppression effect was not the result of a delayed response to IL-2. The PAF-induced suppression was overcome in the presence of PAF antagonists (BN 52021 and BN 50730) but was not modified in the presence of a neutralizing anti-IL-4 antiserum. On the other hand, the IL-4 mediated suppression was totally reversed in the presence of the neutralizing anti-serum and only marginally reversed in the presence of the PAF antagonists. These results indicate that both PAF and IL-4 may exert a number of immunoregulatory actions on human B lymphocyte proliferation and differentiation. They interfere with the stimulation of activated B lymphocytes by IL-2 and could play an important immunoregulatory role in the determination of isotypic regulation in the specific humoral responses.

scholarly journals Helper signals in the plaque-forming cell response to protein-bound haptens.

1983 ◽  
Vol 158 (2) ◽  
pp. 317-333 ◽  
Author(s):  
N W Roehm ◽  
P Marrack ◽  
J W Kappler
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Line ◽  
Interleukin 1 ◽  
Interleukin 2 ◽  
Tumor Cell Line ◽  
Con A ◽  
B Cell Growth Factor ◽  
Nonspecific Factors ◽  
Culture Supernatants

We have demonstrated the ability of a series of murine T cell hybridomas to deliver an antigen-specific, B cell I-region-restricted helper signal in the generation of specific PFC responses to protein-bound haptens. With some hybridomas the elicitation of optimal PFC responses required the addition of nonspecific factors provided by culture supernatants of concanavalin A-stimulated (Con A SN) spleen cells. Using hapten-primed B cells depleted of both T cells and macrophages (Mphi) we have now demonstrated a requirement for three nonspecific factor preparations to substitute for spleen Con A SN in the elicitation of optimal PFC responses. The first preparation was the interleukin 1 containing culture supernatant of the Mphi tumor cell line P388D1, the second the interleukin 2 (IL-2) and B cell growth factor containing Con A SN of the T cell hybridoma FS6-14.13, and the third, the gamma interferon containing Con A SN of the T cell hybridoma FS7-20.6.18. The P388D1 and FS6-14.13 factor preparations were most effective when added at the initiation of culture, while the FS7-20.6.18 factor preparation was most effective when added at 24 h of culture. The activity of FS6-14.13 Con A SN was depleted by incubation with the IL-2-dependent T cell line HT-2. The activity of FS7-20.6.18 Con A SN was abrogated by incubation at pH 2. The results suggest that the generation of PFC responses to protein-bound haptens require at least three nonspecific factors in addition to an antigen/Ia specific helper signal.

scholarly journals Role of interleukin 1 in anti-immunoglobulin-induced B cell proliferation.

1983 ◽  
Vol 157 (5) ◽  
pp. 1529-1543 ◽  
Author(s):  
M Howard ◽  
S B Mizel ◽  
L Lachman ◽  
J Ansel ◽  
B Johnson ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Activation ◽  
Interleukin 1 ◽  
Accessory Cell ◽  
B Cell Activation ◽  
B Cell Growth Factor ◽  
Absolute Dependence

In this report we describe conditions for polyclonal activation of small numbers of highly purified mouse B lymphocytes. Three signals are required for induction of DNA synthesis by the particular subset of small B lymphocytes investigated: a signal delivered by antibodies specific for the IgM receptor expressed on the B cell membrane; a signal delivered by a T cell-derived factor (B cell growth factor [BCGF]); and a signal delivered by the macrophage-derived factor interleukin 1 (IL-1). The conclusion that IL-1 has B cell co-stimulator activity is based on the findings that highly purified preparations of mouse and human IL-1 have the capacity to cause proliferation in B cells treated with anti-IgM and BCGF. Such cultures show an absolute dependence on exogenously added IL-1 when 2-mercaptoethanol is omitted from the medium. BCGF and IL-1 each act in a non-antigen-specific, non-H-2-restricted, synergistic manner. Their requirement is not observed when B cells are cultured at high density, presumably reflecting accessory cell contamination and endogenous factor production under these conditions. The B cell activation induced by these three signals is restricted to proliferation without the production of antibody-forming cells.

scholarly journals Development of a human T-T cell hybridoma secreting B cell growth factor.

1983 ◽  
Vol 157 (1) ◽  
pp. 60-68 ◽  
Author(s):  
J L Butler ◽  
A Muraguchi ◽  
H C Lane ◽  
A S Fauci
Keyword(s):  
T Cell ◽  
B Cells ◽  
Growth Factor ◽  
Cell Growth ◽  
B Cell ◽  
Interleukin 2 ◽  
Lymphocyte Function ◽  
B Cell Growth Factor ◽  
Normal Human

The success of long-term culture of normal human and murine B cells has been hampered by the limited availability of soluble factors capable of maintaining proliferation of activated B lymphocytes. Previous experiments using various culture-derived supernatants in a human system were unable to separate the activities of B cell growth factor (BCGF) and interleukin 2 (IL-2) by immunochemical means. Thus, purified factors with BCGF activity in the absence of IL-2 activity have not been available for study. In the present study, normal human peripheral blood T cells were fused with the hypoxanthine/aminopterin/thymidine-sensitive human T-leukemic cell line, CEM-6. Supernatants from the resulting hybrid cells were tested for the ability to maintain proliferation of normal human B cells in a recently described assay system for human BCGF. Hybrids demonstrating BCGF activity were cloned by limiting dilution. One hybrid clone, 2B11, continued to support proliferation of B cells in both long-term cultures and 6-d assays at a level significantly above that seen with conventionally produced growth factors. No IL-2 activity was found in the supernatant from hybrid 2B11. The hybridoma supernatant was fractionated by gel filtration, and maximum proliferation of B cells was supported by the 18-20,000 mol wt protein fraction. Thus, a human T-T cell hybridoma that has BCGF activity in the absence of any demonstrable IL-2 activity has been developed. Human T-T cell hybridomas secreting discrete immunoregulatory factors should prove to be powerful tools in dissecting the mechanisms of immunoregulation of human lymphocyte function.

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