TBET and CD11c expression in B cells is linked with IgG2c isotype switching, virus-specific immune responses, and humoral autoimmunity. However, the activation requisites and regulatory cues governing TBET and CD11c expression remain poorly defined. Herein we reveal a relationship between TLR engagement, IL4, IL21, and IFNγ that regulates TBET expression in B cells. We find that IL21 or IFNγ directly promote TBET+ expression in the context of TLR engagement. Further, IL4 antagonizes TBET induction. Finally, IL21, but not IFNγ, promotes CD11c expression independent of TBET. Using influenza virus and H. polygyrus infections, we show that these interactions function in vivo to determine whether TBET+ and CD11c+ B cells are formed. These findings suggest that TBET+ B cells seen in health and disease share the common initiating features of TLR driven activation within this circumscribed cytokine milieu.

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The microbiological contamination of drinking water supplies can have serious health consequences for consumers, and this has been dramatically illustrated in recent years by two disease outbreaks in Canada. In this paper, some factors that can influence the microbiological quality of drinking water and its management are examined. Frameworks have been proposed that help to clarify the main elements of health risk assessment and risk management, and, in accordance with these, risks can be logically characterized, evaluated and controlled. A protocol has been developed for microbiological risk assessment and a risk management framework now guides the development of Canada's national guidelines for drinking-water quality. Monitoring of indicator organisms and the application of adequate water treatment are the primary means recommended in the Canadian guidelines to safeguard health from the presence of water-borne pathogens. Understanding the biological characteristics of microbial pathogens is necessary for assessing their impact on community health and appraising the rationale behind drinking-water testing methods and their limitations. Improvements in health surveillance, monitoring, and risk characterization and application of concepts such as multiple barriers (source-to-tap) and total quality management should contribute to better management of the microbiological quality of drinking water.

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