Many pathogens, such as Plasmodium, Mycobacterium tuberculosis (Mtb), HIV, Leishmania and Trypanosoma disseminate and persist in the bone marrow (BM). This poses a conundrum given our current understanding of central tolerance, according to which developing B lymphocytes that bind cognate antigen with high affinity in BM, are deleted from the lymphocyte repertoire or rendered anergic to prevent autoimmunity.

I plan to investigate whether pathogen presence in the BM drives negative selection or anergy in pathogen-specific developing lymphocytes. This would lead to tolerance to the pathogen and could contribute to inefficient acquisition of natural and vaccine-induced immunity that has been observed for many of the pathogens that persist in the BM.