Development and maintenance of a B220- memory B cell compartment.

We have recently demonstrated that a novel somatically mutated B220(-) memory B cell subset rapidly dominates the secondary immune response to (4-hydroxy-3-nitrophenyl) acetyl (NP). Upon adoptive transfer with Ag, B220(+)NP(+) memory B cells produce large numbers of B220(-)NP(+) B cells that can rapidly differentiate into plasma cells. Therefore, it is not clear whether the novel B220(-) memory compartment is a consequence of secondary Ag challenge or whether it develops as a stable memory subset after initial Ag challenge. In this study, we demonstrate the gradual emergence of B220(-)NP(+) B cells in the spleen to maximal numbers 3 wk after initial Ag exposure. Like their B220(+) counterparts, the B220(-) B cells initially appear unmutated at days 5-7; however, the majority rapidly accumulate affinity increasing mutations by days 9-14 of the primary immune response. More extensive cell surface phenotype (GL7(-)BLA-1(-)CD24(-)CD43(+)) argues strongly against germinal center localization and direct analysis in situ places a cohort of B220(-)CD11b(+)NP(+) B cells in the red pulp of the spleen and not in the MZs. These data provide direct evidence for the development of B220(-) memory B cells as a unique cellular consequence of primary Ag exposure. The cellular dynamics and molecular attributes of these unique memory B cells suggest they are distinct cellular products of the germinal center reaction in the primary response and are maintained long-term in the spleen and bone marrow.

Germinal center reaction.

The germinal center reaction is one critical outcome of helper T-cell-dependent antigen-specific B-cell responses. Germinal center reactions are the culmination of an orchestrated series of intercellular information exchanges discussed here as the serial synapsis model of adaptive immunity. The main purpose of the germinal center reaction is the development of B-cell memory through iterative cycles of somatic antigen receptor diversification and the selection of B cells with receptors of best fit. Recent studies provide insight into the regulation of these complex processes in vivo with new information on the cellular organization of the memory B-cell compartment.

Antigen-specific immunity. Th cell-dependent B cell responses.

Helper T cell-regulated B cell responses constitute a major component of the primary immune response to many pathogens. The subsequent development of antigen-specific immune memory is one critical outcome of this primary adaptive immune response. Antigen-specific immunity develops through a series of intercellular information exchanges organized around cognate T cell receptor-peptide/MHC interactions. Here, we discuss these complex molecularevents andtheircellularconsequences in a serial synapsis model of adaptive immunity. Our laboratory has developed strategies to isolate antigen-specific Th cells and B cells to analyze gene expression and cellular function in single responding lymphocytes directly ex vivo. These studies provide insight into the regulation and cellular organization of antigen-specific immune responses in vivo.

Gastric emptying in acute overdose: a prospective randomised controlled trial.

OBJECTIVE: To test the hypothesis that administration of activated charcoal is as efficacious and safe as the combination regimen of gastric emptying plus charcoal in adults after acute oral overdose. DESIGN: Prospective randomised controlled trial, with subjects presenting on odd-numbered dates allocated to the emptied group (E), and those on even-numbered dates to the not-emptied group (NE). SETTING: Princess Alexandra Hospital, Brisbane (a tertiary referral hospital), which serves an adult urban community, between 4 January 1988 and 11 June 1990. SUBJECTS: Consecutive patients (13 years or older) who presented to the Emergency Department after ingesting an overdose of one or more compounds able to be adsorbed by activated charcoal. INTERVENTIONS: All patients received charcoal by the oral or nasogastric route. Those in the E group also had gastric emptying by ipecac-induced emesis or gastric lavage. OUTCOME MEASURES: Clinical course during the first six hours after treatment began, length of hospital stay, complications. RESULTS: 876 patients were eligible for the study. There were no significant differences between the E and NE groups in age and sex distribution, severity of the overdose or other characteristics, except the mean interval between presentation and administration of charcoal (91 min [SD, 52] for E group and 55 [SD, 41] for NE group; P = 0.0001). There were no significant differences between the E and NE groups in outcome, even when the groups were stratified for severity of the overdose or into subgroups that presented sooner or later than one hour after ingestion. CONCLUSIONS: Gastric emptying can be omitted from the treatment protocol for adults after acute oral overdose.

Severe hypoglycaemia. A one-year prospective survey in Wollongong.

A one-year prospective survey of serious hypoglycaemia has been carried out in the Wollongong area. Of insulin-treated patients attending the diabetes clinic, 3.5% had a hypoglycaemic attack of sufficient severity to be referred to hospital. A further 1% received treatment for attacks of hypoglycaemia at home. It is considered that nearly two-thirds of the attacks of hypoglycaemia may have been preventable. Further reductions may be achieved by the better education of patients about their disease.