FIG 4.

Role of BAFF-R during infection. BAFF-R is detected on B cells as early as the immature B cell stage (Fig. 1), and its expression is diminished with the generation of plasma cells. (A) Engagement of BAFF by BAFF-R simultaneously with B cell receptor stimulation promotes the survival and proliferation of pathogen-specific B cells by decreasing the level of the proapoptotic molecule B cell lymphoma 2 (Bcl-2)-homologous antagonist/killer (Bak) and increasing the levels of the prosurvival molecules Bcl-2 and Bcl-x, leading to the enhanced secretion of isotype-switched and unswitched antibodies. (B) Although the mechanism is not elucidated, bacterial polysaccharides from group C meningococcus and group B streptococcus type V have been shown to downregulate the expression of BAFF-R on B cells. BAFF-R levels on B cells are reduced in HIV-infected patients. A decrease in the BAFF-R level is also observed during the acute phase of P. falciparum infection in children as well as experimentally infected adults. The in vivo factors responsible for diminished BAFF-R expression in P. falciparum-infected patients are unknown. Paradoxically, in vitro stimulation of human B cells with the P. falciparum schizont fraction or hemozoin results in increased BAFF-R expression. BAFF-R expression is also downregulated on MZ B cells in T. brucei-infected mice, leading to a decrease in the number of antiparasite IgM⁺ B cells. Unlike malaria and African trypanosomiasis, C. neoformans infection upregulates BAFF-R expression in PBMCs.