• MULTI-FUNCTIONAL EFFECTOR RESPONSES ELICITED FROM IgM MEMORY STEM CELLS

      Winslow, Gary; Kenderes, Kevin (2017)
      The response of memory B cells to challenge infection is fundamental to longterm protection against pathogens. Following challenge, memory B cells can rapidly differentiate into antibody-secreting cells (ASCs) to produce a secondary antibody response. Memory B cells have also been shown to re-enter into germinal centers and undergo additional rounds of affinity maturation. Both the isotype of the B cell and the signals that generated the B cell have been proposed to modulate how memory B cells respond. Initial studies proposed BCR-intrinsic factors are responsible for the differentiation of memory cells. IgM memory cells undergo differentiation in GCs following antigen challenge, while IgG memory cells rapidly differentiate into ASCs. Other studies found no link-between BCR isotype and differentiation. We investigated the differentiation of T-bet+ CD11c+ IgM memory B cells following challenge infection. IgM memory cells differentiated into IgM-producing plasmablasts. Other IgM memory B cells entered germinal centers, underwent class switching, and became switched memory cells. Yet other donor cells were maintained as IgM memory cells. The IgM memory cells also retained their multi-lineage potential following serial transfer. The kinetics of the IgM memory response mimicked the kinetics of the primary response. Thus, IgM memory cells can differentiate into all effector B cell lineages, and undergo self-renewal, properties that are characteristic of stem cells; however, differentiation occurs with the same kinetics of the primary response. We propose that memory B cells have varying degrees of stem cell likeness. IgM memory stem cells retain the most differentiating capacity but respond to challenge similarly to naïve cells, while IgG effector memory cells are primed to rapidly differentiate into IgG ASCs.
    • POSTNATAL ALCOHOL EXPOSURE INFLUENCES ADOLESCENT OLFACTORY RESPONSES TO THE DRUG

      Youngentob, Steven; Harrison, Danielle (2016)
      Human studies illustrate that alcohol exposure while breastfeeding produces a memory of the alcohol scent and modifies behavioral responses to the odor of the drug. The memory and modified behavioral response to alcohol odor suggest that the addictive attributes of alcohol may contribute to patterns of use that increases the risk for alcohol abuse later in life. There is a growing body of evidence that demonstrates prenatal alcohol exposure produces a memory and modified behavioral response to alcohol odor that persists into adolescence, and contributes to alcohol abuse. Given that both postnatal and prenatal alcohol exposure has lasting effects on infants, this study investigated whether rats exposed to alcohol while breastfeeding have a prolonged memory and modified behavioral response to alcohol odor. Long-Evans Hooded rat pups were exposed to alcohol during breastfeeding via the dams' liquid diet. Control animals received ad lib access to an isocaloric, iso-nutritive liquid diet after delivery of their litter up to weaning. To control for effects of malnutrition pair-fed animals were given a control liquid diet equivalent in quantity to the amount their matched animal provided with an alcohol diet consumed the day before. When litters reached adolescence, the behavioral and neurophysiological responses to alcohol odor in a male and female animal from each litter was examined. Relative to controls, animals exposed to alcohol postnatally displayed an altered breathing pattern response to alcohol odor specifically, and an altered breathing pattern and neurophysiological response to novel odorants. The findings of this study builds on the growing body of research that shows the consequences of postnatal alcohol exposure.