Generation of high-affinity IgG is essential against infections and cancer but can cause disease when inappropriately directed. The interplay of T follicular helper cells (TFH) and T follicular regulatory cells (TFR) is critical for production of high-affinity IgG). Here, we improved antigen-specific IgG responses with two interventions that transiently diminished TFR influence. First, mice were administered an antibiotic cocktail (ABX) for an extended period, leading to increased TFH numbers.

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... NP-KLH immunization resulted in higher affinity TNP-specific IgG in ABX mice. In a model of IgG-driven inflammatory nephritis, ABX mice had significantly worse nephritis accompanied by higher affinity antigen-specific IgG, and enriched TFH cells compared to controls. Second, we administered α-PD-1 during immunization to functionally manipulate TFH and TFH cells. This enhanced the affinity of antigen-specific IgG and increased in TFH following immunizations. Thus, altering TFH and TFR ratio during immunization is an appealing strategy to qualitatively improve IgG responses.