After infection with T. brucei AnTat 1.1, C57BL/6 mice lost splenic B2 B cells and lymphoid follicles, developed poor parasite-specific antibody responses, lost weight, became anemic and died with fulminating parasitemia within 35 days. In contrast, infected C57BL/6 mice lacking the cytotoxic granule pore-forming protein perforin (Prf1 -/-) retained splenic B2 B cells and lymphoid follicles, developed high-titer antibody responses against many trypanosome polypeptides, rapidly suppressed parasitemia and did not develop anemia or lose weight for at least 60 days. Several lines of evidence show that T. brucei infection-induced splenic B cell depletion results from natural killer (NK) cell-mediated cytotoxicity: i) B2 B cells were depleted from the spleens of infected intact, T cell deficient (TCR -/-) and FcγRIIIa deficient (CD16-/-) C57BL/6 mice excluding a requirement for T cells, NKT cell, or antibody-dependent cell-mediated cytotoxicity; ii) administration of NK1.1 specific IgG2a (mAb PK136) but not irrelevant IgG2a (myeloma M9144) prevented infection-induced B cell depletion consistent with a requirement for NK cells; iii) splenic NK cells but not T cells or NKT cells degranulated in infected C57BL/6 mice co-incident with B cell depletion evidenced by increased surface expression of CD107a; iv) purified NK cells from naïve C57BL/6 mice killed purified splenic B cells from T. brucei infected but not uninfected mice in vitro indicating acquisition of an NK cell activating phenotype by the post-infection B cells; v) adoptively transferred C57BL/6 NK cells prevented infection-induced B cell population growth in infected Prf1-/- mice consistent with in vivo B cell killing; vi) degranulated NK cells in infected mice had altered gene and differentiation antigen expression and lost cytotoxic activity consistent with functional exhaustion, but increased in number as infection progressed indicating continued generation. We conclude that NK cells in T. brucei infected mice kill B cells, suppress humoral immunity and expedite early mortality.
Trypanosoma vivax causes a wasting disease affecting livestock breeding and agriculture in developing countries of sub-Sahara Africa and South America. Being an extracellular parasite, control of T. vivax has been proposed to be mediated by host antibodies. However, the use of a comparative infection model of wild-type (WT) and tumour necrosis factor (TNF) knockout (TNF(-/-) ) mice shows that the latter is unable to control first-peak parasitaemia, despite the presence of specific antitrypanosome antibodies. In contrast, WT mice parasitaemia peak control coincides with a combined early onset of TNF production and induction of specific antibodies. TNF is mainly produced by liver-associated monocytes and neutrophils. In this study, no other correlation between cellular immunomodulations and peak parasitaemia control was observed, underscoring the importance of the role of TNF in the control of T. vivax infections.
Red blood cells of a type B patient became polyagglutinable eight years ago and have remained so to the present. No infection or other cause for the phenomenon has been diacovered and laboratory studies have established conclusively that the polyagglutinability is distinguishable from Tantigen activation and Irom the effect of periodate treatment in vitro. Cambind 51Cr and Ashby di&rcntial agglutination studies of the survival in Vivo of normal type B donor blood demonstrated that the transfused cells did not become polyag glutinable during more than four months in the patient's circulation. I t is concluded that the underlying abnormality of the patient's red blood cella originates during their formative stage in the bone marrow. The clinical implications of these findings and their possible relationship to the patient's accompanying leukopenia and thrombocytopenia are discussed briefly. POLYACCLUTINABILITY of human red blood cells; i.e., the condition in which the individual's red blood cells are agglutinated by the majority of normal and ABO compatible human sera, can create difficulties in blood typing and testing for compatibility. T h e clinical implications of polyagglutinability and its associated laboratory problems could be dealt with more
The review addresses how infection with Trypanosoma brucei affects the development, survival and functions of B lymphocytes in mice. It discusses (1) the contributions of antibodies to trypanosome clearance from the bloodstream, (2) how B lymphocytes, the precursors of antibody producing plasma cells, interact with membrane form variable surface glycoprotein (VSG), i.e. with monovalent antigen that is free to diffuse within the lipid bilayer of the trypanosome plasma membrane and consequently can cross-link B cell antigen specific receptors by indirect processes only and (3) the extent and underlying causes of dysregulation of humoral immune responses in infected mice, focusing on the impact of wild type and GPI-PLC⁻/⁻ trypanosomes on bone marrow and extramedullary B lymphopoiesis, B cell maturation and survival.
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