Eosinophils Are Not Required for the Induction and Maintenance of an Alloantibody Response

Abstract

Eosinophil-produced cytokines have been shown to participate in the maintenance of antigen-specific plasma cells (PC) in bone marrow (BM), suggesting that eosinophils are required in the development and/or maintenance of alloantibody responses post-transplant. To test this hypothesis, we sensitized eosinophil-deficient ΔdblGATA1 mice and WT control mice with allogeneic splenocytes or with allogeneic heart grafts and compared the kinetics and titers of serum donor-specific antibodies (DSA), as well as BM and spleen CD130+B220low PC populations between groups. Spleen cells from naïve ΔdblGATA1 BALB/c mice contained higher percentages of PC than WT without detectable differences in BM PCs. After sensitization with allogeneic splenocytes, BALB/c ΔdblGATA1 mice contained fewer BM PCs but more splenic PCs compared to controls. These differences were associated with modestly lower titers of serum DSA 4 and 12 weeks after sensitization but secondary immunizations induced similar increases in both groups. Moreover, the kinetics and strength of DSA did not differ in WT and ΔdblGATA1 BALB/c mice transplanted with B6 cardiac allografts, nor did they differ in transplanted ΔdblGATA1 and WT mice on a B6 background. Therefore, eosinophils are not required for alloantibody formation or maintenance in mice and are thus unlikely to be effective targets for antibody desensitization.

Depletion of major pathogenic cells in asthma by targeting CRTh2

“…Therefore, our data indicate that treatment with anti-hCRTh2 in hCRTh2.BAC.Tg mice may only minimally reduce, but not eliminate, plasma cells in the BM. These findings are consistent with data reported by Cravedi et al in eosinophil-deficient dblGATA1 B6 mice where plasma cell numbers showed a minimal to moderate reduction in BM and spleen and no differences in alloantibody titers after immunization (39). Therefore, while reduction in eosinophils may moderately decrease BM plasma cells, it is unlikely to be clinically significant in lowering antibody titers (40).…”

Plasma cells: You are what you eat

“…134,177,178 Genetic knockout studies, however, have provided mixed results, suggesting that plasma cell-intrinsic signaling by these factors might not all be essential in vivo. [185][186][187][188][189] The integration of these signals with primary plasma cell metabolism, however, has been understudied with a notable recent exception. 178,[180][181][182][183][184] The necessity of some of these cell types and secreted cytokines has been disputed, but a common proposed feature of these populations is their ability to secrete pro-survival cytokines and in turn support plasma cell longevity.…”

B cells in transplantation

“…Thus, depletion of eosinophils had moderate success in reducing alloantibody, 52 and inhibiting eosinophil survival by IL-5 blockade has shown some success in experimental models. 53 Such agents are being investigated in clinical trials to treat asthma.…”