While people infected with Leishmania can become refractory to reinfection, human vaccines have not yet been achieved. Glennie et al. identify a population of skin-resident Leishmania-specific memory T cells that produce IFN-γ and recruit circulating T cells to the skin in response to a subsequent parasitic infection. The findings indicate that a successful vaccine may be dependent on generating skin-resident memory T cells for an effective immune response.

The intestinal microbiota is critical for maintaining homeostasis. Dysbiosis, an imbalance in the microbial community, contributes to the susceptibility of several diseases. Many factors are known to influence gut microbial composition, including diet. We have previously shown that fecal immunoglobulin (Ig) A levels are decreased in mice fed a diet free of aryl hydrocarbon receptor (AhR) ligands. Here, we hypothesize this IgA decrease is secondary to diet-induced dysbiosis. We assigned mice to a conventional diet, an AhR ligand-free diet, or an AhR ligand-free diet supplemented with the dietary AhR ligand indole-3-carbinol (I3C). We observed a global alteration of fecal microbiota upon dietary AhR ligand deprivation. Compared to mice on the conventional diet, family Erysipelotrichaceae was enriched in the feces of mice on the AhR ligand-free diet but returned to normal levels upon dietary supplementation with I3C. Faecalibaculum rodentium, an Erysipelotrichaceae species, depleted its growth media of AhR ligands. Cultured fecal bacteria from mice on the AhR ligand-free diet, but not the other two diets, were able to alter IgA levels in vitro, as was F. rodentium alone. Our data point to the critical role of AhR dietary ligands in shaping the composition and proper functioning of gut microbiota.

The effects of B cell-activating factor belonging to the TNF family (BAFF) on B cell maturation and survival in the mouse are relatively well understood. In contrast, little is known about the role of BAFF in B cell development in other mammals, such as rabbits, that use GALT to develop and maintain the B cell compartment. We examined the expression and requirement of BAFF and a proliferation-inducing ligand (APRIL) during peripheral B cell development in young rabbits. By neutralizing BAFF and APRIL in neonates with a soluble decoy receptor, transmembrane activator calcium modulator and cyclophilin ligand interactor-Fc, we found a marked reduction in the number of peripheral B cells, but found no change in the bone marrow (BM) compartment. In the appendix, the size and number of proliferating B cell follicles were greatly reduced, demonstrating that although BAFF/ APRIL is dispensable for B cell development in BM, it is required for B cell development in GALT. We found that all rabbit B cells expressed BAFF receptor 3, but did not bind rBAFF, suggesting that the BAFF-binding receptors (BBRs) are bound by endogenous soluble BAFF. Further, we found that B cells themselves express BAFF, suggesting that the soluble BAFF bound to BBRs may be endogenously produced and stimulate B cells in an autocrine fashion. Additionally, we propose that this chronic occupancy of BBRs on B cells may provide a tonic and/or survival signal for the maintenance of peripheral B cells in adults after B lymphopoiesis is arrested in BM.

The peripheral B cell compartment in mice and humans is maintained by continuous production of transitional B cells in the bone marrow (BM). In other species however, including rabbits, B lymphopoiesis in the BM abates early in life and it is unclear how the peripheral B cell compartment is maintained. We identified transitional B cells in rabbits and classified them into T1 (CD24hiCD21lo) and T2 (CD24hiCD21+) B cell subsets. By neutralizing BAFF in vivo, we found an arrest in peripheral B cell development at the T1 B cell stage. Surprisingly, T1 B cells were present in GALT, blood and spleen of adult rabbits, long after B lymphopoiesis was arrested. T1 B cells were distinct from their counterparts in other species because they are proliferating and the Ig genes are somatically diversified. We designate these newly described cells as T1d B cells and propose a model in which they develop in GALT, self-renew, and continuously differentiate into mature B cells, and thereby maintain peripheral B cell homeostasis in adults in the absence of B lymphopoiesis.

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Summary In species other than mouse, little is known about the origin and development of marginal zone (MZ) B cells. Using cross-reactive antibodies, we identified and characterized splenic MZ B cells in rabbits as CD27+CD23−. In rabbits in which organized GALT was surgically removed at birth, we found only CD23+ follicular (FO) B cells and almost no CD27+ MZ B cells in the spleen, indicating that GALT is required for the development of splenic MZ B cells. These findings lead us to suggest that commensal microbiota contribute to development of MZ B cells.

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