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TB Wars

B Cells, the Forgotten Weapon

In tuberculosis research, B cells get no respect. “B cells got a bad rap more than a century ago when physicians began experimenting with serum therapies for TB,” says John Chan, M.D., professor of medicine and of microbiology & immunology at Einstein and attending physician in infectious diseases, department of medicine, at Montefiore.


P.J. Maglione and John Chan, M.D.
The blood’s serum contains antibodies, which are produced by immune cells called B cells. The idea behind serum therapy is to protect people against infection. This approach worked well against some infectious diseases.

But studies in the late 1800s found that antibodies offered inconsistent protection against TB, leading to skepticism regarding their usefulness.

Dr. Chan and his Einstein colleagues are among the small coterie of TB investigators who believe not only that B cells deserve a second look but that they may be essential for creating better TB therapies and vaccines that are more effective.

Dr. Chan first got interested in B cells after noticing unusual aggregates of cells in the lungs of mice infected with M. tuberculosis. To his surprise, those collections of cells were chock full of B cells.


Immunofluorescence staining reveals a B-cell aggregate in a patient with pulmonary tuberculosis. The surfaces of the B cells are stained red and the nuclei are stained blue.
Image by Soumya Chakravarty, M.D., Ph.D.
“The body’s immune response to TB was supposedly driven by T cells, not B cells,” he says. “But we saw that humans with active TB had the same B-cell aggregates in lung tissue as mice did, which led us to wonder, ‘What are those B cells doing?’”

Plenty, it turns out. In studies of mice, Dr. Chan and P. J. Maglione, an M.D./Ph.D. student in his lab, showed that B cells:

  • form a significant part of lung granulomas (clumps of immune cells that create a physical barrier against the spread of bacteria);
  • modulate the functions of T cells, which are critical in defending against M. tuberculosis;
  • regulate the inflammatory response in the lungs of infected hosts; and
  • boost the effectiveness of the BCG vaccine, the only approved TB vaccine.

“While more needs to be learned about the role of B cells in TB, there are already enough data to suggest that this arm of immunity should not be overlooked,” says Dr. Chan. Today, he and his colleagues are in the middle of a five-year study, funded by the National Institute of Allergy and Infectious Diseases, to shed more light on how B cells help fight TB.

 

 
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