Director of Immunobiology/Associate Professor of Medicine Massachusetts General Hospital/Harvard Medical School Charlestown, Massachusetts, United States
Abstract Text: Bacillus Calmette-Guérin (BCG), a >100-year-old vaccine derived from Mycobacterium bovis, is known for its broad protective abilities against diverse infectious and autoimmune diseases. Recent studies show that BCG also promotes long-lasting blood sugar control in individuals with type 1 diabetes (T1D) and protection against COVID-19 with high vaccine effectiveness. BCG efficacy in humans is dependent on BCG strain and multiple BCG vaccinations change the immune system to provide clinical benefits including infectious disease protection and durable glucose control. Although previous studies have attributed these benefits to acute monocyte modifications through innate immune “training,” we now show that BCG treatment is associated with immune training of B cells in individuals with T1D. In this open-label study, we administered 2 doses of BCG (1 × 10^5 CFU; strain BCG Japan) to 31 T1D patients and longitudinally measured changes in the B cell compartment using flow cytometry studies. B cells and B cell markers (CD19+, CD21+, CD10+, and CD319+) were studied. Over the course of two years, we identified a significant and sustained increase in the Median Fluorescence Intensity (MFI) of CD10 and CD319 on the surface of B cells, markers that are present on early-/pre-B cells and plasma B cells, respectively. The percentage of CD10+ and CD319+ B cells was also significantly increased compared to both patients’ baseline levels and to nondiabetic controls. The previously reported broad protection of BCG vaccination for diverse infectious diseases might be attributed to BCG priming the B cell compartment.
