FIG 2.

Role of TACI during infection. (A) TACI is mostly expressed on mature B cells and plasma cells. Its elevated expression levels on MZ B cells and B1 cells lead to augmented antibody (Ab) responses against TI-II antigens. Together with the multivalent cross-linking of B cell receptor by polysaccharides, the engagement of TACI by BAFF or APRIL increases activation-induced cytidine deaminase (AID) transcript levels, leading to a polysaccharide-specific antibody isotype switch to IgA and IgG. TACI activation also induces the generation of plasma cells. The requirement for TACI expression to maintain plasma cells also extends to responses against T cell-dependent (TD) antigens. TACI has been shown to regulate the magnitude and kinetics of T follicular helper (Tfh) cell development and germinal center (GC) formation. The consequence of TACI deficiency is mostly detrimental to the survival of plasma cells after immunizations or infections. Citrobacter rodentium infection of TACI-deficient mice, however, leads to an enhanced clearance of the bacteria and higher levels of antibacterial antibodies with increased affinity. (B) TACI expression can be modulated by pathogens. Whereas C. neoformans and capsular polysaccharides (PS) from a meningococcal type C strain and a group B streptococcus serotype V strain blunt B cell responses to BAFF and APRIL by strongly suppressing TACI expression, B cells from HIV- or P. falciparum-infected patients manifest elevated levels of TACI. (C) Expression of TACI in macrophages has been shown to be required for M1 polarization. IL-12 secreted from M1 macrophages induces Th1 responses and IFN-γ production. IFN-γ promotes macrophage inflammatory responses, including nitric oxide (NO) generation, to control intracellular L. major infection. TI, T cell independent; ICOS-L, inducible costimulator ligand; CSR, class switch recombination.