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Biomedical subjects

H S Micklem

Publications and source records attributed to H S Micklem.

At least 55 records · Page 3Linked to original sources

Long-term immunoglobulin G production by transplanted thymus cells.

Two sublines of CBA/H mice congenic for the Igl allotype locus were used to study donor-allotype IgG2a concentrations in the serum of mice injected intravenously with thymus cells. High concentrations (up to several mg/ml) were found in x-irradiated recipients (exposed to 650 rad, or to 900 rad with a restorative injection of fetal liver cells). The highest concentrations were seen 1-2 months after injection, but detectable quantities were still present in most individuals after 377 days. No donor-allotype Ig was detected in non-irradiated recipients. Cell for cell, lymph node cells were about as efficient as thymus cells at transferring IgG production. Although pluripotent hematopoietic stem cells were found in the thymus, their concentration (about 10(-8)) was too low to account for the results. It is suggested that the thymus contains B lymphocytes, or their precursors, with considerably greater powers of self-maintenance and expansion than are possessed, on average, by the B lymphocytes in lymph nodes.

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75SeL-selenomethionine: a new isotopic marker for lymphocyte localisation studies.

L-selenomethionine (SeM), an analogue of methionine containing Se, is incorporated by mouse and rat lymphocytes in vitro: labelled with 75Se (75SeM) it emits gamma-rays distinguishable in energy from those of 125I and 51Cr. The usefulness of 75SeM for lymphocyte localisation studies was investigated. Both B and T cells incorporated 75SeM. Reutilization of the isotope in the mouse after injection of killed cells or allogeneic cells into immunized recipients was 1-2% of the injected dose. The immunocompetence of labelled mouse T and B cells was assessed in irradiated recipients, no effect of 75SeM incorporation being found. The distribution of labelled lymphocytes from various tissues in syngeneic recipients was found to be comparable to that previously obtained with 51Cr.

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Age-related changes in localization of injected radiolabelled lymphocytes in the lymph nodes of antigen-stimulated mice.

The localization of i.v. injected syngeneic lymph node cells, radiolabelled with 51Cr or 75Se-L-selenomethionine, was studied in male CBA/H mice aged between 3 and 30 months. The following results were obtained. (1) Localization of cells from young adult donors was greater in the s.c. lymph nodes of old than of young recipients, the main increase being between 15 and 17 months of age. Increases in lymph node weight and DNA-synthesis were also seen at this time; but the rise in cell localization was significant even when calculated per unit of tissue weight. Splenic localization either declined slightly with age or, like the liver, showed no significant change. (2) Local antigenic stimulation by a single injection of sheep erythrocytes into one front footpad, 24 hr before lymph node cell injection, resulted in increased localization in the regional lymph nodes of 3-17 month old, but rarely of 24-30 month old mice. (3) No consistent differences in localization were observed between lymph node cells from 4-month and 25-month old donors. Both age-related and antigen-related increases in cell localization were at least partly attributable to an enhanced rate of entry of lymphocytes from the blood to the lymph nodes. Although the changes underlying the decline in antigen-related localization of cells in old recipients have still to be clarified, it is probable that the defective immune responses of old mice result partly from this decline.

Aging↗

Compartments and cell flows within the mouse haemopoietic system. I. Restricted interchange between haemopoietic sites.

Two chromosomally distinguishable haemopoietic cell populations were injected into lethally irradiated syngeneic recipients. The presence or absence of the T(14;15)6Ca reciprocal translocation (indicated by T6 marker chromosomes) did not affect the proliferation of a population. Wide disparities were found in the proportions of the two donor cell populations between animals and between the right and left femora of individual animals. This suggest (i) that there is, at most, a very limited interchange of proliferating cells and their precursors between the marrow of different bones; and (ii) that the number of clones proliferating in the bone marrow at any one time must be rather small; there was evidence that this number depended in part on the number of haemopoietic cells injected. Exchange between the mitotically active cell populations of spleen, thymus, lymph nodes and bone marrow was also limited, as shown by significant disparities in the proportions of the two donor populations proliferating in the different tissues of individual mice.

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Compartments and cell flows within the mouse haemopoietic system. II. Estimated rates of interchange.

Part-body irradiated CBA mice were injected with CBA-T6 bone marrow. In this way a predominantly donor population was established in the femora while the marrow of the humeri remained largely (average 94%) of host origin. In animals examined cytologically up to 2 years later, no tendency was observed for the proportion of donor cells in the humeri to increase. Splenectomy had no effect on this. When femoral bone marrow from the experimental mice was injected into lethally (whole-body) irradiated recipients, cells originating from the primary host repopulated the lymph nodes to a disproportionate extent. Equilibration between the cell populations of femora and humeri occurred after re-exposure to 600 rad whole-body irradiation, but not after 100 rad or 350 rad; thus, regeneration of damaged bone marrow involved a significant contribution from extrinsic stem cells only after the highest dose of radiation. The data are compatible with an inflow of at most ten effective stem cells per humerus per day from the blood, and suggest a much lower figure. This means that few if any of the stem cells of peripheral blood enter the bone marrow and found haemopoietic clones. Evidence is adduced for the existence of a proliferating lymphoid sub-population in the bone marrow, contributing some 5-10% of the observed mitoses. The mitotic cells in the lymph nodes are replaced from marrow-derived progenitors at an estimated rate of 4-5%/day. The relevant data for the thymus are more variable, but suggest an average figure of 8-11%/day. Earlier data from mouse parabionts suggest a lower rate of inflow to the thymus.

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Maternal immunization to paternal antigens in multiparous mice.

Mice of the CBA strain which had given birth to five litters sired by males of a different H-2 type (C57BL/10) showed evidence of immunization to paternal antigens, in that the numbers of lymphocytes forming alloclusters with paternal erythrocytes were significantly elevated. On the other hand, the graft-versus-host responsiveness of maternal splenic lymphocytes to paternal antigens remained virtually unchanged, showing only a slight increase at Day 8 of the assay.

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