Differences in mouse and human nonmemory B cell pools.

Identifying cross-species similarities and differences in immune development and function is critical for maximizing the translational potential of animal models. Coexpression of CD21 and CD24 distinguishes transitional and mature B cell subsets in mice. In this study, we validate these markers for identifying analogous subsets in humans and use them to compare the nonmemory B cell pools in mice and humans, across tissues, and during fetal/neonatal and adult life. Among human CD19(+)IgM(+) B cells, the CD21/CD24 schema identifies distinct populations that correspond to transitional 1 (T1), transitional 2 (T2), follicular mature, and marginal zone subsets identified in mice. Markers specific to human B cell development validate the identity of marginal zone cells and the maturation status of human CD21/CD24 nonmemory B cell subsets. A comparison of the nonmemory B cell pools in bone marrow, blood, and spleen in mice and humans shows that transitional B cells comprise a much smaller fraction in adult humans than mice. T1 cells are a major contributor to the nonmemory B cell pool in mouse bone marrow, in which their frequency is more than twice that in humans. Conversely, in spleen, the T1:T2 ratio shows that T2 cells are proportionally ∼ 8-fold higher in humans than in mice. Despite the relatively small contribution of transitional B cells to the human nonmemory pool, the number of naive follicular mature cells produced per transitional B cell is 3- to 6-fold higher across tissues than in mice. These data suggest differing dynamics or mechanisms produce the nonmemory B cell compartments in mice and humans.

Apparent seizure and atrial fibrillation associated with paliperidone.

PURPOSE: A case of apparent seizure and atrial fibrillation associated with paliperidone is reported. SUMMARY: A 46-year-old man arrived at the emergency room (ER) via ambulance. Earlier that morning, his wife observed him awakening in a panic, drifting back to sleep, and then subsequently awakening in a panic with an apparent seizure lasting one to two minutes. The episode included tongue biting and urinary incontinence. His medical history included bipolar disorder, diabetes mellitus, hyperlipidemia, and hypertension. The patient's medications included metformin, insulin glargine, insulin lispro, simvastatin, enalapril, escitalopram, lamotrigine, and clonazepam and had not changed for many months except for the recent addition of paliperidone four days before his arrival at the ER. Electrocardiography revealed atrial fibrillation, a ventricular rate of 151 beats/min, a Q-Tc interval of 461 msec, and no significant changes in the ST segment or T wave. He had no chest pain, and all other laboratory test results and vital signs were normal. The patient was admitted for evaluation and given a single oral dose of potassium chloride. Diltiazem i.v. was administered with resultant conversion to normal sinus rhythm, after which the patient's heart rate and Q-Tc interval normalized. The patient was discharged after one day. CONCLUSION: A man taking paliperidone and multiple other drugs experienced atrial fibrillation and a possible seizure. Although these are known adverse effects of atypical antipsychotics, it is unusual to have both events occur concurrently and with low-to-average dosages, and these events have not been associated with paliperidone in published case reports.