The rate of pathogen elimination determines the extent and consequences of an infection. In this context, the spleen with its highly specialized lymphoid compartments plays a central role in clearing blood-borne pathogens. Splenic marginal zone B cells (MZ), by virtue of their preactivated state and topographical location, join B1 B cells to generate a massive wave of IgM producing plasmablasts in the initial 3 days of a primary response to particulate bacterial antigens. Because of the intensity and rapidity of this response, combined with the types of antibodies produced, splenic MZ and B1 B cells endowed with a "natural memory" provide a bridge between the very early innate and the later appearing adaptive immune response.

Mouse splenic B cells can be separated based on their distinctive expression of cell surface antigens. Marginal zone (MZ) B cells are CD38high CD21high CD23low/-, while follicular (FO) B cells are CD21int CD23int and newly formed (NF) B cells are CD21dim/- CD23-. Exploiting these phenotypic distinctions, we isolated the three B cell subsets and assessed their other phenotypic differences and functional capabilities in vitro. FO B cells proliferate more than the other B cell subsets in response to either IgM or CD38 cross-linking. MZ B cells proliferate better than FO B cells when stimulated with lipopolysaccharide (LPS), sub-optimal levels of LPS and CD38 cross-linking or CD40 ligation. When NF, FO and MZ B cells were stimulated with either LPS or LPS and interleukin-4, MZ B cells secreted more IgM and IgG3 than the other two subsets. Similarly, calcium fluxes measured within MZ B cells are larger in amplitude and more sustained after B cell receptor cross-linking than those found in the other two subsets. Collectively, these results indicate that CD38high CD21high CD23low/- MZ B cells are specially suited to play a unique role in response to antigens delivered to the MZ area.

Our study documents the clinical and electrographic findings in 42 patients with medically refractory occipital lobe epilepsy, who underwent surgery at the Montreal Neurological Institute between 1930 and 1991, and the evolving manner in which those patients were studied by successive generations of investigators. In more than two-thirds of the patients the clinical manifestations indicated the occipital onset of the seizures. Seventy-three percent experienced visual aurae, of which elementary hallucinations were the most common and 12 also had ictal blindness. Other occipital manifestations included: contralateral eye deviation, blinking, a sensation of eye movement and nystagmoid eye movements. Intra-operative cortical stimulation elicited a habitual aura in 37% of 29 patients. Lateralizing clinical features were seen in almost two-thirds of patients: contralateral head deviation occurred in half, 59% had visual field defects contralateral to the epileptogenic area and 64% had abnormal imaging studies ipsilateral to the side of surgery. More than one-third of patients exhibited more than one seizure type, suggesting ictal spread to temporal or frontal lobe: 50% had typical temporal lobe automatisms, and 38% exhibited focal motor seizure activity. Surface electroencephalogram (EEG) recordings showed posterior temporal-occipital epileptiform discharges in 46% of patients. Only 18% had electronegative spiking limited to 01 or 02. Large epileptogenic areas were often found on intracranial recording with depth electrodes and on electrocorticography. Pre-excision electrocorticography spiking was restricted to the occipital lobe in only 13 out of 34 patients. More often spiking also involved the posterior temporal and posterior parietal regions. Twenty-three patients underwent only occipital resections; five had only temporal resections, so as to preserve the visual fields, and the remaining 14 patients had extensive resections, which included the posterior temporal or posterior parietal regions. A follow-up period of 1 to 46 yrs (mean 17 yrs) was available for 37 patients. Forty-six percent became seizure free and 21% had a significant reduction in seizure frequency. A better outcome was observed in those patients in whom there was no post-resection electrocorticographic or surface EEG epileptiform discharge, or who exhibited an occipital lobe lesion.

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