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The delay in parasite-specific B cell development leaves people in malaria endemic areas vulnerable to repeated infections. Here, we investigated the role of transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), a molecule involved in the generation of antigen-specific antibody secreting cells, in host response to non-lethal infection. We found that TACI deficiency not only resulted in higher peak parasitemia levels in challenged mice, but also led to a delay in parasite clearance and anti- Merozoite Surface Protein 1(C-terminal 19-kDa fragment [rMSP-1]) protein and anti-rMSP-1 and anti- IgG antibody development. There was also a delay in the generation of splenic high affinity antibody secreting cells that recognize rMSP-1 protein as compared to wild-type mice. Interestingly, coinciding with the delay in parasite clearance there was a delay in the resolution of T follicular helper (T) cell and germinal center (GC) B cell responses in TACI -/- mice. The persistence of T and GC B cells is likely a result of enhanced interaction between T and GC B cells because inducible costimulator ligand (ICOSL) expression was significantly higher on TACI -/- GC B cells than wild-type cells. The difference in the kinetics of GC reaction appeared to also impact the emergence of plasma cells (PC) because there was a delay in the generation of TACI -/- mice PC. Nevertheless, following the recovery from infection, TACI -/- and wild-type mice were both protected from a rechallenge infection. Establishment of protective B cell response was responsible for the resolution of parasitemia because B cells purified from recovered TACI -/- or wild-type mice were equally protective when introduced to naïve wild-type mice prior to challenge. Thus, despite the increased susceptibility of TACI -/- mice to infection and a delay in the development of protective antibody levels, TACI -/- mice are able to clear the infection and resist rechallenge infection.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237915 | PMC |
| http://dx.doi.org/10.3389/fimmu.2018.02612 | DOI Listing |
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