PBMC from patients with autoimmune diseases and from normal controls were studied for the expression of several cellular oncogenes. Gene expression was assessed by Northern blot analysis of poly(A)+ RNA obtained from leukapheresis samples. Patients with SLE expressed significantly more c-myc protooncogene RNA than did normal controls. Increased expression of the N-ras protooncogene was found in that subset of patients whose autoimmune disease was very active. Cells from individuals with SLE, but not from those with other autoimmune illnesses, showed significantly decreased levels of the c-myb and c-fos protooncogenes. To examine the implications of these findings, B and T cells were purified from apheresis samples donated by normal volunteers. When mitogen was used to activate the B cells in vitro, their pattern of protooncogene expression changed to resemble that found in freshly isolated cells from lupus patients. These results suggest that the differences detected in the expression of protooncogenes by patients with SLE may be due to the abnormal activation of their B cells in vivo. The pattern of protooncogene expression found in patients with other autoimmune illnesses is consistent with the activation of additional cell types in those diseases.
The evolution of a 2n = 34 combined Robertsonian translocation strain Rb(5.19)1Wh/(6.15)1Ald/(8.17)HEM is described. Homozygotes had three large ring translocation bivalents at M I and regular meiotic disjunction at M II. Male and female F1· heterozygotes had similar frequencies of abnormal meiotic disjunction at M II, but aneuploid embryos were more frequent in (F1♂ X NIH GP ♀) crosses (25.6%) than (F1 ♀ X GP ♂) crosses (13.5%) at 10 days’ gestation. It could not be determined whether this discrepancy was genetic in origin or due to limitations in the techniques of M II analysis. Rb(5.19), as well as Rb(6.15) or (8.17), contributed to the aneuploidy, although previous M II analysis of singly heterozygous Rb(5.19)/+ males demonstrated comparatively regular meiotic disjunction. Trisomic embryos were not detected beyond 10 days in five (F1 ♀ X GP ♂) crosses, suggesting that their survival in F1 females is limited. The ratios of the different types of balanced embryos from the (F1 X GP) crosses indicated random meiotic segregation of the three translocation chromosomes in triple heterozygotes. Analysis of complementary groups of balanced embryos from the same crosses also demonstrated lack of preferential segregation of the translocations; embryos with translocations and those with their corresponding homologous acrocentrics were equally frequent. Triploid embryos (3.3 %) were also detected in (F1♂ X NIH GP ♀) crosses. The translocations and Y chromosome served as paternal markers, permitting its origin to be determined in two of three cases (dispermy). One growth-retarded triploid had a distinctive anomaly: failure of lens induction and lack of optic cup development. The combined strain provided a complex of markers for determining polyploidy mechanisms, as well as a common genetic background for comparing behavior of the three translocations at M I.
Resting B cells enter and progress through the G1 phase of the cell cycle in response to low concentrations (1 to 5 micrograms/ml) of anti-IgM antibodies. Commitment to enter S phase requires the presence of a fivefold to 50-fold higher concentration of anti-IgM. These and other results strongly suggest that two separately controlled events are involved in B cell activation. The current studies demonstrate that B cells incubated with high concentrations of anti-IgM from the initiation of culture become independent of additional anti-IgM approximately 10 hr before entry into S phase. We have designated this anti-IgM independent portion of the G1 phase of the cell cycle as G1 beta, whereas the earlier phase is referred to as G1 alpha. Furthermore, low concentrations of anti-IgM are sufficient for progress through early portions of G1 alpha, but high concentrations are required for the last 4 to 8 hr (G1 alpha') if the cells are to go through the rest of the cell cycle. Removal of anti-IgM at any time during G1 alpha causes prompt cessation of the size enlargement that accompanies progress through G1. Such cells retain their size and their relative place in G1 for periods of at least 17 hr and recommence movement through G1 alpha phase when anti-IgM is readded. Thus, B cells may exist in states of partial activation and must possess a mechanism to integrate the amount of stimulatory signal they have received; they enter a commitment period for S phase only when that signal passes some threshold value.
NZB mice were exposed from birth to a diet either adequate or deficient in copper. By age 6 wk the mice exposed to the copper-deficient diet showed symptoms characteristic of copper deficiency (anemia, hypoceruloplasminemia, and achromatrichia). The splenic lymphocytes from the copper-deficient group had reduced numbers of cells expressing the following surface markers: Ly-5, Ly-1, B-220, and sIg. Less than 10% of the splenic lymphocytes in this group were cycling, as determined by flow cytometry analysis. The spontaneous 96-h anti-ss-DNA levels in the copper-deficient group were lower than those in the control group. The exogenous colony-forming units (CFUs) were significantly enhanced in the copper-deficient mice. The decreased splenic lymphoid populations, decreased anti-ss-DNA titers, and increased exogenous CFUs in the copper-deficient mice appear to be due to an increase in erythropoiesis at the expense of lymphopoiesis.
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