Autophagy is dispensable for B-cell development but essential for humoral autoimmune responses.

To gain new insight into the role of B-cell autophagy, we generated two novel mouse models deficient for the autophagy-related gene (Atg)5, one from the outset pro-B cell stage (Atg5(f/-) Mb1 cre) and the other in mature B cells only (Atg5(f/-) CD21 cre). We show that autophagy is dispensable for pro- to pre-B cell transition, but necessary at a basal level to maintain normal numbers of peripheral B cells. It appears non-essential for B-cell activation under B-cell receptor stimulation but required for their survival after lipopolysaccharide stimulation that drives plasmablast differentiation and for specific IgM production after immunization. Results obtained using Atg5(f/-) CD21 cre × C57BL/6(lpr/lpr) autoimmune-prone mice show that B-cell autophagy is involved in the maintenance of anti-nuclear antibody secretion, elevated number of long-lived plasma cells, and sustains IgG deposits in the kidneys. Thus, treatments specifically targeting autophagy might be beneficial in systemic autoimmune diseases.

Use of transfer impedance measurements for clinical assessment of lung mechanics.

Respiratory transfer impedance (Ztr) measured using the forced oscillation technique requires virtually no patient cooperation and provides a noninvasive approach for acquiring data reflective of lung mechanics. Also, model analysis of Ztr provides reliable estimates of separate airway and tissue properties (1), but only if data out to 64 Hz are acquired. The current study evaluated the clinical utility of Ztr from 1-80 Hz for assessing the degree and type of impaired lung function. Spirometry and Ztr measurements were made on 37 individuals: 11 healthy subjects and 26 patients with lung disease including chronic obstructive pulmonary disease (COPD), asthma, lung cancer, and sarcoidosis. Over the entire patient group, 12 were also smokers. We first established normal ranges for several Ztr features and model estimated mechanical properties. The COPD and smokers groups showed significant differences in portions of their Ztr spectra from that of the healthy group. Key Ztr spectral features included R0, the frequency at which the real part of impedance is zero; and Re4, the real part of impedance at 4 Hz. The key model parameter was airway resistance, Raw. We found Raw, Re4, and R0 to be significantly elevated during disease (p < 0.0005) and to significantly decrease with bronchodilator therapy (p < 0.025). Moreover, we found moderate to strong correlations between R0, Raw, and Re4 versus FVC and R0 versus FEV1. After bronchodilator, changes in R0, Re4, and Raw were correlated with changes in several spirometric indices. The R0 feature has not been previously evaluated since it is typically above 32 Hz (well above 32 Hz in diseased individuals) and not encompassed in previous clinical studies.