[Effects of multipotent hematopoietic stem cell inhibitory factor on formation of immune response to viral antigen]. / Vliianie faktora, ingibiruiushchego proliferatsiiu polipotentnoi stvolovoi krovetvornoi kletki na formirovanie immunnogo otveta k virusnomu antigenu.

An immunostimulating effect of PIF was studied. The augmentation of antibody production to Coxsackie A13 virus as well as protective effect during influenza infection have been found out in mice after PIF injections. An immunostimulating effect of PIF after SRBC immunization of mice has been also revealed. Possible mechanisms of immunostimulating effect of PIF are discussed.

[Expression of erythroid differentiation antigens on mononuclear cells of peripheral blood in neoplastic progression of non-Hodgkin's malignant lymphoma]. / Ekspressiia éritroidnykh differentsirovochnykh antigenov na mono- nuklearakh perifericheskoi krovi pri opukholevoi progressii nekhodzhkinskikh zlokachestvennykh limfom.

High level expression of erythroid differentiation antigens on peripheral blood mononuclear cells associated with increased BFUe number has been identified in a malignant lymphoma patient. A possible pathogenetic role of such disturbance in leukemogenesis has been considered.

[The regulation of hematopoietic stem cell proliferation and differentiation (CFU-S) during antigenic exposure]. / Reguliatsiia proliferatsii i differentsirovki gemopoéticheskikh stvolovykh kletok (KOEs) pri antigennom vozdeistvii.

Hemopoietic stem cell (CFUs) proliferation is controlled by regulatory activities (stimulator and inhibitor) produced by bone marrow macrophages. Previously it has been shown that antigen administration stimulates CFUs proliferation. The data obtained in this study show the possible mechanism of antigen-induced stimulation of CFUs proliferation. 3-4 days after antigen injection bone marrow cells of BDF1 mice cease to produce inhibitory activity in contrast to similar cells of control animals. Therefore, increased CFUs proliferation in immunized mice can be due to decreased production of inhibitory activity and resulting abundance of stimulating factors. In BAlB/c mice CFUs proliferation is not changed after antigen injection and their bone marrow cells continue to synthesize inhibitory substances. Differentiation of CFUs into committed blood precursor cells may depend on the proliferation level in CFUs population since activation of CFUs proliferation in immunized BDF1 mice is accompanied by a decreased number of CFU-GM and CFU-M but an increased number of BFU-E. It should be noted that intact BAlB/c mice show a high level of CFUs proliferation similar to that of immunized BDF1 mice.

Species-nonspecific action of soluble immunosuppressive factor produced by murine immature erythroid cells.

Immature murine erythroid cells have natural suppressor cell activity suppressing in vitro mouse plaque-forming cell response and LPS-stimulated proliferative response of mouse spleen cells. A cell population enriched by erythroid precursors can produce a soluble activity with similar suppressive abilities. This erythroid suppressor activity (ErSF) has a low Mr (1 to 10 kDa). It can suppress both IgM and IgG secretion of PWM-stimulated human B cells and inhibit the proliferative response of PWM-stimulated human B lymphocytes, thereby indicating a species-nonspecific type of action. Antigen-induced mouse PFC response and mitogen-stimulated mouse and human B cell proliferation were inhibited dose dependently by the addition of ErSF, which did not significantly reduce cell viability, however. Kinetic studies showed that ErSF suppressed Ig secretion and proliferation of mitogen-stimulated B lymphocytes in all culture periods. The suppressive effect of ErSF on B cell proliferation was indirect, requiring the presence of IL-2 (but not of IL-1 alpha, IL-1 beta, or BCGF). In the presence of IL-2, the proliferative response of SAC-stimulated B cells was suppressed by ErSF when added at all time intervals studied but was maximal when ErSF was added on the third day of culture. The role of suppressor factor produced by immature murine erythroid cells in the phenomenon of "natural suppression" has been discussed.

[Erythroid immunosuppressor cells (Er suppressors) and their role in the regulation of immunity]. / Immunosupressornye kletki éritroidnogo riada Er-supressory i ikh rol' v reguliatsii immuniteta.

It is a review of works concerning the new mechanism of immunoregulation by immature erythroid cells (Er-suppressors). Er-suppressors producing humoral activity were shown to be capable of inhibiting B cell proliferation, production of immunoglobulins and humoral immune response both in mice and man. By certain characteristics Er-suppressors seem to be an logous to natural suppressors described by many authors. It is common knowledge that natural suppressors play a substantial role in the regulation of early stages of lymphocytopoiesis. Erythropoiesis disturbances may lead to the appearance at the periphery of immature precursors from bone marrow and to the suppression of B cell proliferation in the peripheral blood and lymph nodes. Detection of Er-suppressors in the patients' peripheral blood by immunofluorescence with monoclonal antibodies allows one to study their role in autoimmune and lymphoproliferative diseases and secondary immune deficiencies and to elaborate new methods of the diagnosis and treatment of these diseases.

[Suppressive effect of the blast cells of AKR strain mice on antibody formation in vivo and lymphocyte proliferation in vitro]. / Supressivnyi éffekt blastnykh kletok myshei linii AKR na antiteloobrazovanie in vivo i proliferatsiiu limfotsitov in vitro.

Blast cells obtained from the "erythropoietic spleen" of FG-stimulated young mice and cells accumulating in the spleens of preleukemic AKR mice have a marked suppressive effect on spontaneous and mitogen-induced proliferation of young mouse splenocytes in vitro and suppress the development of humoral immune response in immunized recipients during syngeneic transfer in vivo. Some disturbances in erythron system in preleukemic AKR mice manifested in the accumulation of immature erythroid precursors which are suppressors of immunocompetent lymphocytes are suggested to be a pathogenetic link in the development of leukemia.

[Interrelation of the dynamics of antigen intake into bone marrow and the proliferation of hematopoietic stem cells]. / Vzaimosviaz' mezhdu dinamikoi postupleniia antigena v kostnyi mozg i proliferatsiei stvolovykh krovetvornykh kletok.

As it is previously shown (Tsyrlova et al., 1986), the level of humoral immune response is not only determined by the reaction of peripheral lymphoid system on antigenic effect, but also is bound up with the observed stem blood cell (SBC) proliferation in bone marrow (Frindel et al., 1976, Kozlov et al., 1982). Dynamics of label accumulation in bone marrow was examined when injecting antigen--sheep red blood cells labeled by radioisotope 51Cr, 125I. The peak of label accumulation in bone marrow, accompanied by the increase in proliferative SBC, was observed on the 3rd day after antigen injection. Furthermore in the course of immunization 51Cr labeled macrophage assortment was changed in time in such a way that a greater number of macrophages was accumulated in bone marrow on the 3rd and 4th days in the immunized animals in comparison with the intact ones. The macrophages in bone marrow are likely to take part in antigen uptake and to mediate its effect on SBC proliferation.

The effect of haemopoietic stem cell proliferation on the humoral immune response in mice.

A study was made of the effect of humoral factors, isolated from bone marrow cell (BMC) supernatant fluid and capable of modifying CFU-S proliferation, on the generation of IgM plaque-forming cells (PFC) against sheep red blood cells (SRBC) in mice after adoptive transfer. Adoptive transfer of BMC, preincubated with the humoral factor RBME-III, which stimulates CFU-S proliferation, was shown to suppress the splenic PFC generation in recipients; treatment of BMC with a further factor NBME-IV, which inhibits CFU-S proliferation, was followed by augmentation of PFC generation. Similar effects were obtained while studying the IgM PFC generation in the bone marrow of mice after secondary immunization when relevant factors were injected, in vivo, 24 hr following primary immunization. The results of adoptive transfer experiments indicate that populations of T- and B-cells are not the targets for the action of CFU-S proliferation regulatory factors. These factors are shown to modulate the erythroid differentiation of CFU-S. The possibility of quantitative modification of immune response parameters with the help of bone marrow factors that influence the proliferation and differentiation of CFU-S is discussed.

[Proliferative activity of the hematopoietic stem cell in antigenically stimulated splenectomized mice]. / Proliferativnaia aktivnost' stvolovoi krovetvornoi kletki u splenéktomirovannykh myshei pri antigennom vozdeistvii.

Proliferative activity of hemopoietic bone-marrow stem cells has been studied in splenectomized mice in response to sheep red blood cells (2 X 10(8], pneumococcal polysaccharide (100 micrograms) and lipopolysaccharide E. coli (100 micrograms) injections. Spleen and its lymphoid cellular elements were shown to be of great importance for the regulation of the functional activity of hemopoietic stem cells under the antigenic influence.

Colony-forming activity of pluripotent stem cells in tolerant mice following antigen exposure.

The effect of sheep red blood cells (SRBC) and human red blood cells (HRBC) on the number of CFU-S in the bone marrow and spleen of (CBA X C57BL/6)F1 mice tolerant to SRBC was examined. The number of bone marrow and spleen CFU-S in SRBC tolerant mice was increased after injection of HRBC. After challenge with SRBC, CFU-S number was elevated in the spleen but not in the bone marrow. Thus, the mechanism of CFU-S activation in response to antigen exposure is different in the bone marrow and spleen.

[Colony-forming activity of hematopoietic stem cells in tolerant mice as affected by antigens]. / Kolonieobrazuiushchaia aktivnost' stvolovykh krovetvornykh kletok u tolerantnykh myshei pri antigennom vozdeistvii.

The effect of sheep red blood cells (SRBC) and human red blood cells (HRBC) on the amount of CFUs in the bone marrow and spleen of (CBA X C57BL/6) FI SRBC-tolerant mice was studied. The increase in the number of bone marrow and spleen CFUs was demonstrated in SRBC-tolerant mice injected with HRBC. Using SRBC test injection the increase in CFUs amount was observed in the spleen, but not the bone marrow, where the amount of CFUs remained unchanged.

Hemopoietic stem cell proliferative activity in B-mice under the influence of antigenic stimulation.

The influence of thymus dependent and thymus independent antigens on proliferation of CFU-S in B-mice bone marrow was investigated. The process of CFU-S proliferative activity increases after the injection of both antigens and is mediated in part by B-lymphocytes.

Hemopoietic stem cells "age" structure revealed by the exogenous colony forming method.

The number of colony forming units in mice following the transplantation of cells of bone marrow, spleen and embryonal liver, forming exogenous spleen colonies on 5, 8 and 11 days has been determined. It has been shown that stem cell subpopulation forming colonies on 5 day (CFUs-5) was notable for lower capacity for self maintenance, and contained predominantly by erythroid colonies, these CFUs-5 were mainly in embryonal liver and less in reduced in the hemopoietic populations in mice.

[Experimental model for studying the participation of bone marrow cells in antibody formation]. / Eksperimental'naia model' dlia izucheniia uchastiia kletok kostnogo mozga v antitelogeneze.

Participation of bone marrow cells in the production of IgM antibody forming cells (AFC) in the primary immune response to sheep red blood cells (SRBC) in C57Bl/6 and BDA/2 mice was studied. The animals of this line differed in sensitivity to preoral benz(a)pyren (BP) injection. After BP injection a toxical injury of bone marrow cells was observed for two days in DBA 2 mice but was not marked in C57Bl/6 mice. In the former it was followed by a 10-fold decrease of IgMAFC, while no profound changes were noticed in the immune response of the latter. A new model is offered for the evaluation of bone marrow cell participation. A suggestion is made concerning some connection of immunodepression in the bone marrow with the change of the stem hemopoietic precursor differentiation.