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Biomedical subjects

R Benner

Publications and source records attributed to R Benner.

At least 181 records · Page 10Linked to original sources
PubMed1981

Regulation of the "spontaneous' (background) immunoglobulin synthesis.

The number of mature cytoplasmic immunoglobulin containing cells (C-Ig cells) in various lymphoid organs of the mouse was studied as a function of antigenic load and the presence of T cells. Both antigen and T-cell deprivation decreased the number of C-Ig cells (plasma blasts and plasma cells). The absolute C-Ig cell numbers were minimal in germfree nude mice, intermediate in specific pathogen-free (SPF) nude mice and in germ-free thymus-bearing mice, and the largest in SPF thymus-bearing mice. The bone marrow was the organ where this picture was most strikingly examplified. In germfree C3H mice raised on a synthetic diet the bone marrow of 3 out of 4 mice tested did not show any C-Ig cell. None of them had C-Ig cells in the mesenteric lymph nodes. The Ig class distribution of the C-Ig cells and the incidence of C-Ig cells positive for more than one Ig heavy-chain isotype ("double producers') were also highly dependent upon the antigenic load and the presence of T cells. C-IgM cells were well represented in all groups of mice. Appreciable numbers of C-IgA cells were only found in SPF thymus-bearing mice. The absolute number, but not the relative number, of C-IgG cells followed the same pattern. The percentages of double producers in the various lymphoid organs were largest in germfree nude mice, intermediate in SPF nude mice and in germfree thymus-bearing mice, and minimal in SPF thymus-bearing mice. From these studies we conclude that the background synthesis of IgG and IgA in not intentionally immunized mice is virtually completely dependent on stimulation of the immune system by external antigens, in contrast to the production of IgM.

Animals↗
PubMed1981

The mechanism of thymus-dependent antibody formation in bone marrow.

During the primary immune response of mice to i.v. administered thymus-dependent antigens the spleen is the major site of localization of antibody-producing plaque-forming cells (PFC). During the secondary response, on the other hand, large numbers of PFC not only appear in the spleen, but also in the bone marrow. By inducing B memory cells with a DNP-carrier complex and activating the DNP-specific B memory cells with the same hapten conjugated to a heterologous carrier, we show in this paper that B memory cells, but not necessarily T memory cells, must be present before booster immunization for PFC to appear in the bone marrow. The origin of the PFC that appear in the bone marrow during secondary type immune response was studied in parabiotic mice consisting of members congenic for the Igh-1 locus. From analysis of the allotype of antibodies produced by PFC in the marrow of such pairs of parabionts it appeared that antibody formation in bone marrow is dependent on the immigration into the marrow of B memory cells activated in peripheral lymphoid organs. Consistent with such a migration of activated cells, radioautographic studies in guinea pigs demonstrated an influx of newly formed mononuclear cells into the bone marrow via the blood stream during the first 3 days after intravascular antigen administration.

Animals↗
PubMed1981

Frequency analysis of immunoglobulin V-gene expression and functional reactivities in bone marrow B cells.

Frequency of immunocompetent B cells in bone marrow has been determined in vitro under culture conditions that allow the development in vitro under culture conditions that allow the development of every growth-inducible B cell into a clone of IgM-secreting PFC. Three limiting dilution culture systems were employed: a specific helper assay with SRBC as antigen and using activated T helper cells, a nonspecific helper assay using Con A-induced factors as a source of help, and polyclonal activation with LPS. From unseparated, normal C57BL/6J bone marrow 1 in 2200 to 1 in 2820 B cells were induced to form a clone of PFC to SRBC in each of the 3 systems. This corresponds to a frequency of 1 SRBC-specific clone in every 900 IgM-secreting LPS-reactive clones. The frequencies of specific plaque-forming B cell clones in terms of LPS-reactive B cells was 1 in 36 for NNP1-SRBC, 1 in 58 for TNP30-SRBC, 1 in 75 for NIP1-SRBC, and 1 in 230 for TNP3-SRBC. These frequencies of v-gene expression in bone marrow B cells are of the same magnitude as the corresponding frequencies for splenic B cells. Bone marrow B cells are also fully susceptible to stimulation by antigen in combination with either specific or nonspecific T cell help, as well as polyclonal activation by LPS, since every 3rd Ig-positive cells in marrow could be induced to form a clone of IgM-secreting cells. There is thus no difference in immunocompetence between surface Ig-bearing B cells from bone marrow and spleen.

Animals↗
PubMed1981

The bone marrow: the major source of serum immunoglobulins, but still a neglected site of antibody formation.

Immunoglobulin (Ig) secreting cells occur in all lymphoid tissues, including the bone marrow (BM). There are important differences between the various organs with respect to their number of Ig-secreting cells and the heavy chain isotype distribution of the secreted Igs. Furthermore, both distribution patterns depend on age. Early in life most Ig-secreting cells are localized in spleen and lymph nodes. In adults, however, the majority of all Ig-secreting cells of the individual are localized in the BM. Immunization can lead to the appearance of substantial numbers of antibody-forming cells in BM. The kinetics of the BM response are different from the response in the peripheral lymphoid tissues. Shortly after immunization most antibody-forming cells occur in the peripheral lymphoid tissues, but later on, especially during secondary type responses, most antibody-forming cells are localized in the BM. Apparently, antibody formation is regulated in such a way that peripheral lymphoid tissues respond rapidly, but only for a short period, whereas the BM response starts slowly, but takes care of a long-lasting massive production of antibodies to antigens which repeatedly challenge the organism.

Age Factors↗
PubMed1980

Different target antigens for T-cell subsets acting synergistically in vivo.

After allogenic transplantation of lymphoid cells into immunologically incompetent recipients, a graft-versus-host (GvH) reaction can occur. The original observation that the GvH reaction is mediated by two interacting types of T cell has led to the proposal that T cells must be subdivided into two subpopulations according to life span and migratory properties. These consist of T1 cells, which are short-lived, sessile cells sensitive to adult thymectomy (ATx), and T2 cells, which are long-lived, recirculating cells sensitive to anti-thymocyte serum (ATS). T1-T2 cooperation has also been demonstrated in vitro in murine and rat mixed lymphocyte culture. The question arises as to whether these T-cell subpopulations are activated by different or identical parts of the major histocompatibility complex (MHC). We report here that for optimal development of the anti-host immune response in a murine GvH reaction, T2 cells have to be amplified by T1 cells. The former cells are activated by a set of MHC gene products that are expressed mainly on immunological cells (H-2I-coded antigens), whereas the latter recognize a different set of MHC gene products that are expressed on almost all cells of the mouse (H-2K/D-coded antigens).

Animals↗
PubMed1980

Serum immunoglobulins in nude mice and their heterozygous littermates during ageing.

Serum immunoglobulin (Ig) levels were investigated in 6, 40 and 110 week old congenitally athymic (nude) mice and their heterozygous littermates. Concentrations of IgM, IgG1, IgG2a, IgG2b, IgG3 and IgA were determined by rocket electrophoresis. At 6 weeks of age, IgM was the most prominent serum Ig in both nude and heterozygous mice. Except for IgM and IgG3, some nude mice displayed unquantifiable levels of some of the other Ig classes or subclasses. At this age, the average levels of the various Ig classes and/or subclasses did not differ significantly between the two groups of mice. At the ages of 40 and 110 weeks, most nude mice showed serum Ig spectra in which all classes and subclasses were present. Young (6 week) and middle-aged (40 week) nude mice generally showed a wider variation in Ig levels than did their heterozygous littermates. The most striking differences between aged nude mice and aged heterozygous mice were: (a) the generally decreased levels of IgG2a, IgG2b and IgA; (b) the frequent occurrence of increased serum levels of IgG1; and (c) the increased incidence of homogeneous Ig components ('paraproteins') in the sera of nude mice.

Aging↗
PubMed1980

Kinetics of recovery of serum Ig levels and of cytoplasmic Ig positive cells in various lymphoid organs of nude mice after thymus transplantation.

The long-term effects of thymus transplantation in nude mice were studied with regard to the number of cytoplasmic immunoglobulin positive plasmablasts and plasma cells (C-Ig cells) in various lymphoid organ and their immunoglobulin (Ig) class distribution profile. These data were correlated with the serum Ig levels of the same mice. Four weeks after thymus transplantation, the number of C-Ig cells in the spleen of nude mice had increased two- to three-fold over that found in normal nude mice and normal heterozygous littermates of the same age. This overshoot subsided at 8 weeks after thymus transplantation. The increase of the C-Ig cell number in the other lymphoid organs tested (bone marrow, mesenteric lymph nodes and Peyer's patches) started later than in spleen, and did not show a clear overshoot. Almost complete recovery of the C-Ig cell pattern to that of normal littermates was found 32 weeks post-transplantation. Analysis of the Ig class distribution of the C-Ig cells showed that the increase of the C-Ig cell numbers after thymus transplantation in nude mice was almost exclusively confined to IgG1, IgG2 and IgA. The increase of C-IgG1 and C-IgG2 cells in spleen and bone marrow correlated with a simultaneous increase of the serum IgG1 and IgG2 levels, suggesting that these organs are the major source of serum IgG in young adult mice.

Animals↗
PubMed1979

Serum and secretory immunoglobulin levels in preleukaemic AKR mice and three other mouse strains.

Levels of IgM, IgC1, IgG2 AND IgA were determined in serum and milk of AKR mice, which spontaneously develop lymphoma at 6--14 months of age. As a reference C3H, CBA and C57BL mice were studied. Of the four mouse strains studied AKR had the lowest serum and secretory IgA levels. The values of the other immunoglobulins in AKR mice were comparable to those of CBA mice. C3H and C57BL mice had significantly higher immunoglobulin levels. Serum of lactating mice showed fairly decreased IgG1 and IgG2 levels as compared with non-lactating mice, probably due to transudation into the milk. The serum IgM and IgA levels were not consistently affected by lactation.

Allergy and Immunology↗