An “unconventional” immune response now identified by scientists from the Hackensack Meridian Center for Discovery and Innovation (CDI) is a potential new avenue for the development of new vaccines for tuberculosis (TB), according to a new publication.
Marginal zone B (MZB) cells are a natural response to TB infection that has long been overlooked – and which may be a welcome new target that could be boosted through new vaccines to better fight and prevent of the disease, according to the new publication in the newspaper Cell references.
“Our results indicate that B cells skew their immune landscape toward MZB cells to perform anti-TB regulatory functions, highlighting the importance of antibody-independent mechanisms of B cells in the control of infectious diseases, a previously overlooked mechanism “, the authors write.
Using high-dimensional flow cytometry, the team mapped the progression of the infection in an animal model. They showed that B cells shifted their immune landscape towards MZB cells.
Through detailed monitoring of this shift, MZB cells showed higher activity and expression of a memory-like phenotype in response to infection. In turn, this modulated cytokine patterns and subsequently enhanced cellular immunity.
“This discovery opens a new avenue in TB vaccine development, suggesting that targeting B cells for their regulatory functions could be a promising new strategy,” the authors add.
The paper’s authors were led by CDI scientists: Chen-Yu Tsai Ph.D., Ariel Aptekmann, Ph.D. Thomas Dick, Ph.D. and Martin Gengenbacher, Ph.D.
Gengenbacher has studied the genus Mycobacteria including tuberculosis for most of his career. In 2021 he was awarded $6.4 million from the NIH to pursue an innovative new TB vaccine idea. Since the only available TB vaccine, Bacille Calmette-Guérin, or BCG, is very unreliable, Gengenbacher and his team proposed improving BCG by engineering it to stimulate B cell growth and communication, an important part of the immune system. With this strategy, researchers aim to develop a second-generation TB vaccine that will provide reliable and durable protection against new infections and may even help treat existing TB infections by complementing antibiotic therapy.
Source:
Journal Reference:
Tsai, C.-Y., et al. (2024). Splenic marginal zone B cells limit Mycobacterium tuberculosis infection by modulating cytokine pattern and cell-mediated immunity. Cell references. doi.org/10.1016/j.celrep.2024.114426.
