Publications

B cells are key components of cellular and humoral immunity and, like all lymphocytes, are thought to originate and renew from hematopoietic stem cells (HSCs). However, our recent single-HSC transfer studies demonstrate that adult bone marrow HSCs do not regenerate B-1a, a subset of tissue B cells required for protection against pneumonia, influenza, and other infections. Since B-1a are regenerated by transfers of fetal liver, the question arises as to whether B-1a derive from fetal, but not adult, HSCs. Here we show that, similar to adult HSCs, fetal HSCs selectively fail to regenerate B-1a. We also show that, in humanized mice, human fetal liver regenerates tissue B cells that are phenotypically similar to murine B-1a, raising the question of whether human HSC transplantation, the mainstay of such models, is sufficient to regenerate human B-1a. Thus, our studies overtly challenge the current paradigm that HSCs give rise to all components of the immune system.

By convention, airborne particles ≤0.1 μm (100 nm) are defined as ultrafine particles (UFPs). UFPs can comprise a large number of particles in particulate matter with aerodynamic diameters ≤2.5 μm (PM). Despite the documented respiratory health effects of PM and concerns that UFPs might be more toxic than larger particular matter, the effects of UFPs on the respiratory system are not well-described. Even less is known about the respiratory health effects of UFPs among particularly vulnerable populations including children. We reviewed studies examining respiratory health effects of UFPs in children and identified 12 relevant articles. Most (8/12) studies measured UFP exposure using central ambient monitors, and we found substantial heterogeneity in UFP definitions and study designs. No long-term studies were identified. In single pollutant models, UFPs were associated with incident wheezing, current asthma, lower spirometric values, and asthma-related emergency department visits among children. Also, higher exhaled nitric oxide levels were positively correlated with UFP dose among children with asthma or allergy to house dust mites in 1 study. Multivariate models accounting for potential co-pollutant confounding yielded no statistically significant results. Although evidence for a relationship between UFPs and children's respiratory is accumulating, the literature remains inconclusive. Interpretation of existing data is constrained by study heterogeneity, limited accounting for UFP spatial variation, and lack of significant findings from multi-pollutant models.