The kinetics of growth of peripheral blood cells in tissue culture are described. There was a rapid increase of cells in DNA synthesis beginning at 24 hours and by 72 hours 40-45 per cent of the cells were in DNA synthesis. Mitotic rates of ∼ 1 per cent/hour were seen after 72 hours in cultures. Studies with tritiated thymidine and colchicine indicated that these cells represent transformed lymphocytes and do not arise from the cells in DNA synthesis at time zero or from any other small population of cells.
Analysis of 1684 inpatient and 884 outpatient peripheral blood counts revealed the following: (1) The absolute lymphocyte count declines sharply from 5000/microletre to 2000/microletre in the first two decades, remains constant for three decades, then declines at an accelerated rate beginning in the 40s, to reach 1500/microletre at age 90. (2) The absolute granulocyte count does not show age-dependent variation, remaining essentially constant throughout life. (3) The values of absolute lymphocytes are indistinguishable for ambulatory or hospitalized subjects except for higher absolute lymphocyte counts in hospitalized children in the first decade. (4) The data support other evidence for declining cellular and humoral immunity in aging man.
A patient presented with lymphoblastic lymphoma in lymph-nodes and chronic myelogenous leukemia (CML) in narrow and peripheral blood. All marrow and unstimulated peripheral blood cells contained the Philadelphia chromosome[t(9:22)]. Lymphoma cells were analyzed by flow cytometry and were identified as T cells (CD2+CD5+CD7+CD34+). All fresh lymphoma cells contained the t(9:22) translocation. Cultures of purified peripheral blood T and B cells and specifically stimulated NK cells revealed that 59% of the B cells, 10% of the NK cells, and none of the normal T cells contained the translocation. The lack of translocation in normal peripheral T cells is attributed to their long lifespan. No rearrangement of immunoglobulin or T cell receptor beta or gamma genes was found in either the leukemia or lymphoma cells. Analysis of the DNA from cryopreserved lymphoma biopsy showed clonal rearrangement within the common breakpoint cluster region of the bcr gene identical to the bcr rearrangement in DNA from leukemia blood cells. The data support the concept that T and B cells originate in the patient's totipotent stem cell from which the CML is also derived.
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