No abstract

Transgenic mice expressing the Pim-1 kinase are predisposed to develop T-cell lymphomas with a long latency period of about 7-9 months. However, the exact functional basis of the oncogenic activity of Pim-1 remains obscure. C57BL/6 mice homozygous for the lpr mutation develop a well-described lymphoproliferative syndrome at about 26-30 weeks of age. This syndrome is characterized mainly by the accumulation of abnormal T cells in lymph nodes because of the lack of Fas receptor-induced apoptosis. We rind that backcross ofE.-Pim-1 transgenics (mice with a transgene that carries the mouse Pim-l gene under the transcriptional control of the immunoglobulin heavy chain gene enhancer EIs) into lpr/lpr mice results in strong acceleration of lymphoproliferation and dramatic enlargement of lymph nodes. In addition, we show here that cultured lymph node cells from E,u-Pim-1 lpr/lpr mice are rescued from rapid apoptosis that normally occurs in nontransgenic lpr cells in vitro. We also present evidence that CD4+/CD8 double-positive thymocytes from lpr/lpr mice are sensitive to dexamethasone-induced apoptosis, although lpr/lpr mice lack the Fas receptor. In contrast, E,u-Pim-1 lpr/lpr animals show considerable protection from dexamethasone-induced apoptosis. These results show that Pim-1 can strongly accelerate lymphoproliferation through inhibition of apoptosis and thereby provide first insight into the functional basis for the oncogenic activity of Pim-l.Mice homozygous for the lpr mutation show enlargement of cervical lymph nodes because of a proliferation of abnormal yet nonmalignant T cells that bear B220 and Thy-1.2 but lack CD4 and CD8 surface markers (for review, see refs. 1 and 2).

No abstract

The immune response to foreign erythrocytes was studied in vitro. Two subpopulations of cells were prepared. One was a population of bone marrow-derived spleen cells, taken from thymectomized, irradiated, and bone marrow-reconstituted mice; there was evidence that most of the precursors of the PFC had been present in this cell population, but few PFC developed in cultures of these cells alone in the presence of immunogenic erythrocytes. Another cell suspension was made from spleens of mice which had been irradiated and injected with thymus cells and erythrocytes; these cells were called educated T cells. The two cell suspensions together allow the formation of PFC in the presence of the erythrocytes which were used to educate the T cells, but not in the presence of noncross-reacting erythrocytes. If bone marrow-derived cells and T cells were kept in culture together with two different species of erythrocytes, and if one of the erythrocytes had been used to educate the T cells, then PFC against each of the erythrocytes could be detected.

A novel monoclonal anti-immunoglobulin is described which in soluble form is comparable to lipopolysaccharide in its ability to induce DNA synthesis in populations of resting B cells. It inhibits lipopolysaccharide-induced B cell maturation to immunoglobulin secretion while not suppressing mitogen-induced proliferative responses. B cells from C3H/HeJ mice are stimulated as well as those from C3H/Tif mice demonstrating that the induction capacity of this monoclonal antibody does not involve functional lipopolysaccharide receptor molecules.

Deuteron spin–lattice relaxation experiments on α-crystallized toluene-d3 are reported. It is shown that the two distinct methyl groups existing in this crystal can be identified by 2H–T1 experiments. The temperature dependence of the broadenings is found to be different, particularly in an intermediate temperature range, where transitions to the second excited librational state dominate the dynamics for one type of methyl group. For the second type, the crossover from a low temperature behavior to a ‘‘quasiclassical’’ regime takes place in a very narrow temperature range. The apparent activation energies are compared to the known transition energies of protonated toluene.

We have developed an experimental system for linking information on cell-free transcription and translation products from cDNA clones with data obtained from hybridization signals from complex probes. The work described in this paper consists of two distinct processes, one being the construction of a system of clonal addresses and the other the identification of expressed genes involved in the studied processes. We describe the use of this system to identify genes involved in thymus development. Complex probes from fetal thymuses (GD15, 17 and newborn) of Balb/c mice were used to identify genes, which are up- or downregulated during the process of differentiation. The full set of information is available in the Clone-base of the Basel Institute for Immunology and will be retrievable from the website of the collaborating laboratories.

The nature and sequence of events leading to stimulation of B lymphocytes and to clonal proliferation and differentiation of antibody-secreting cells are not yet known. One of the proposed mechanisms involves the action of complement on C3b receptor-bearing B lymphocytes (1). In these experiments we investigated the effect of isolated C3b on DNA synthesis and blast cell formation in mouse lymphocyte cultures . This approach was taken since C3b is an activator of the alternate complement pathway (2, 3) and when bound to C3b receptors could effect receptor-bearing cells through complement activation .The first suggestion for complement involvement during the induction of a humoral immune response was provided by the observation that, in vivo, reduction of serum C3 levels by cobra venom factor inhibited the development of thymus-dependent humoral antibody formation (4) . The role of C3 in the thymus-dependent antibody response was explained in terms of receptor-bound C3 augmenting cell cooperation and antigen presentation (5) . Other investigators showed that, in vitro, T-cell mediated or mitogen-triggered antibody formation could only be elicited in the presence of C3-sufficient serum (6, 7) . Furthermore, activation of the alternative complement pathway by cobra venom factor could substitute for T cells in the immune response to thymus-dependent antigens . The authors assumed that this effect was due to direct interaction of "activated" C3 with the C3b receptor of B lymphocytes .In this report we demonstrate stimulation of DNA synthesis and blast formation in murine lymphocyte cultures by C3b. The results suggest that the stimulation is caused by activation of the alternative complement pathway by receptor-bound C3b . Materials and MethodsMice . DBA/2 and BDF, mice were bred in our colony. Male C3H/HeJ and C3HeB/FeJ mice were bought from Jackson Laboratories (Bar Harbor, Maine) . Congenitally athymic mice (nu/nu) were kindly provided by Dr . J . Watson (The Salk Institute, San Diego, Calif.) .