T. brucei infection reduces B lymphopoiesis in bone marrow and truncates compensatory splenic lymphopoiesis through transitional B-cell apoptosis.

TitleT. brucei infection reduces B lymphopoiesis in bone marrow and truncates compensatory splenic lymphopoiesis through transitional B-cell apoptosis.
Publication TypeJournal Article
Year of Publication2011
AuthorsBockstal, V., Guirnalda P., Caljon G., Goenka R., Telfer J. C., Frenkel D., Radwanska M., Magez S., and Black S. J.
JournalPLoS Pathog
Volume7
Issue6
Paginatione1002089
Date Published2011 Jun
Type of Articleparasites
ISSN1553-7374
KeywordsAnimals, Antibodies, Protozoan, Antibody Formation, Antigenic Variation, Apoptosis, Bone Marrow, Cells, Cultured, Immunologic Memory, Lymphopoiesis, Mice, Mice, Inbred C57BL, Precursor Cells, B-Lymphoid, Spleen, Trypanosoma brucei brucei, Trypanosomiasis, African, Variant Surface Glycoproteins, Trypanosoma
Abstract

African trypanosomes of the Trypanosoma brucei species are extracellular protozoan parasites that cause the deadly disease African trypanosomiasis in humans and contribute to the animal counterpart, Nagana. Trypanosome clearance from the bloodstream is mediated by antibodies specific for their Variant Surface Glycoprotein (VSG) coat antigens. However, T. brucei infection induces polyclonal B cell activation, B cell clonal exhaustion, sustained depletion of mature splenic Marginal Zone B (MZB) and Follicular B (FoB) cells, and destruction of the B-cell memory compartment. To determine how trypanosome infection compromises the humoral immune defense system we used a C57BL/6 T. brucei AnTat 1.1 mouse model and multicolor flow cytometry to document B cell development and maturation during infection. Our results show a more than 95% reduction in B cell precursor numbers from the CLP, pre-pro-B, pro-B, pre-B and immature B cell stages in the bone marrow. In the spleen, T. brucei induces extramedullary B lymphopoiesis as evidenced by significant increases in HSC-LMPP, CLP, pre-pro-B, pro-B and pre-B cell populations. However, final B cell maturation is abrogated by infection-induced apoptosis of transitional B cells of both the T1 and T2 populations which is not uniquely dependent on TNF-, Fas-, or prostaglandin-dependent death pathways. Results obtained from ex vivo co-cultures of living bloodstream form trypanosomes and splenocytes demonstrate that trypanosome surface coat-dependent contact with T1/2 B cells triggers their deletion. We conclude that infection-induced and possibly parasite-contact dependent deletion of transitional B cells prevents replenishment of mature B cell compartments during infection thus contributing to a loss of the host's capacity to sustain antibody responses against recurring parasitemic waves.

DOI10.1371/journal.ppat.1002089
Alternate JournalPLoS Pathog.
PubMed ID21738467
PubMed Central IDPMC3128123
Grant ListR03AI073461 / AI / NIAID NIH HHS / United States
Research group: