B cell tissue residence in the human TB lung and their impact on the TH1 or TH2 response

B cells form aggregates in the human lung following Mycobacterium tuberculosis (Mtb) infection. This phenomenon is also prevalent in animals including mice and non-human primates. Female mice have both larger and more numerous aggregates in their lungs and our preliminary data supports a similar trend of tissue-resident memory B cells in humans. Intriguingly males are more susceptible to TB in mice and humans. The specific role of B cells in the human lung has not been investigated, however, despite this apparent association with TB susceptibility. 

Therefore, Robert Krause and his team aim to study these aggregates and propose that they are functionally organised structures of cells that facilitate B cell maturation at the site of disease, the human lung. In addition, there is evidence that B cells themselves can influence other immune cells such as T cells and macrophages in their response to disease. B cells could therefore bias the immune response in the lung either toward a protective TH1 response or a TH2 response which facilitates the spread of TB. The team aim to use new microscopy techniques that will allow them to identify where the B cells are found in the lung tissue and which specific genes they are expressing, allowing them to link their function to a spatial context.

Understanding the function of B cells during TB in the human lung and how they might influence protective immune responses could inform new treatment strategies or provide biomarkers to predict disease progression.

SANTHE is an Africa Health Research Institute (AHRI) flagship programme funded by the Science for Africa Foundation through the DELTAS Africa programme; the Bill & Melinda Gates Foundation; Gilead Sciences Inc.; and the Ragon Institute of Mass General, MIT, and Harvard.