T. brucei Infection Reduces B Lymphopoiesis in Bone Marrow and Truncates Compensatory Splenic Lymphopoiesis through Transitional B-Cell Apoptosis

PLoS Pathogens

Guy Caljon¹  Deborah Frenkel¹  Samuel J. Black²  Stefan Magez²  Viki Bockstal²  Radhika Goenka²  Janice C. Telfer³  Patrick Guirnalda³  Magdalena Radwanska⁴ 

[1] Department of Molecular and Cellular Interactions, VIB, Brussels, Belgium;Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, Massachusetts, United States of America;Laboratory for Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium;Unit of Veterinary Protozoology, Institute of Tropical Medicine, Antwerp, Belgium

关键词: B cells;    Trypanosoma;    Apoptosis;    Trypanosoma brucei gambiense;    Spleen;    Parasitic diseases;    Trypanosoma brucei;    Bone marrow cells;   

DOI  :  10.1371/journal.ppat.1002089

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY