Impaired proliferative responses of peripheral blood B cells from splenectomized subjects to phorbol ester and ionophore.
The responses of peripheral blood B cells to mitogenic stimulation were examined in 12 splenectomized subjects without residual splenic function, as determined by pitted erythrocyte counts. These were compared to a group of healthy controls matched for age and sex. Polyclonal anti-immunoglobulin evoked a normal transient elevation in intracellular free Ca2+ in splenectomized subjects, thereby suggesting that the early events of the signal transduction pathway are not impaired. However, mitogenic stimulation by pre-treatment with phorbol ester and culture in presence of a calcium ionophore (Ionomycin) resulted in reduced uptake of 3H-thymidine and subsequent proliferation. Nevertheless, entry into the mitotic cycle, as assessed by expression of Ki67, was slightly, but not significantly impaired. Unlike in normal controls, where up to 7% of freshly-isolated B cells were Ki67+, almost no Ki67+ peripheral B cells were observed in splenectomized subjects. The data are consistent with the hypothesis that peripheral B cells in splenectomized subjects are in a reduced state of activation compared with normal controls and require additional growth factor stimulation before they can undergo mitosis.
Foster
P N
PN
Department of Clinical Medicine, St James's University Hospital, University of Leeds, UK.
Trejdosiewicz
L K
LK
D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D015220:Calcium Channels / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006801:Humans; D007476:Ionophores / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D008938:Mitosis; D010703:Phorbol Esters / Q000494:pharmacology*; D013156:Splenectomy
D015220:Calcium Channels; D007476:Ionophores; D010703:Phorbol Esters