IL-10 Differentially Regulates IgE and IgG4 Production through Indirect Effects on Nave B Cells
Sunday, March 6, 2016: 4:45 PM
Concourse Foyer (Convention Center)
Adora A. Lin, MD, PhD, Thomas B. Nutman, MD
Rationale: Allergen immunotherapy (and control of parasitic helminth-associated pathology) is associated with decreased antigen/allergen-specific IgE and increased antigen/allergen-specific IgG4. Although T cell-derived IL-10 appears to contribute by altering the balance of antigen/allergen-specific IgE/IgG4, mechanisms mediating this alteration are largely unknown. Previous studies of IL-10’s effects on the preferential switch from IgE to IgG4 have been conducted primarily with peripheral blood mononuclear cells (PBMCs) and less commonly with purified whole B cell populations. The present study sought to explore how (and whether) IL-10 mediates preferential isotype switching to IgG4 using highly purified naïve B cells.

Methods: Human PBMCs and highly purified (>93%) naïve B cells (CD3-CD19+CD20+CD21+CD27-) were each cultured under a variety of conditions (combinations of IL-4, IL-10, and anti-CD40). Immunoglobulin (Ig) IgG and IgE isotypes were quantified from culture supernatants using ELISA or multiplexed immunoassays.

Results: Consistent with previous studies, in PBMC cultures, IL-4 induced the production of both IgE and IgG4 (IgG4:IgE ratio mean 2.8, range 0.4-8.7). The addition of IL-10 reduced the IL-4-induced IgE production and concurrently enhanced the induction of IgG4 such that the IgG4: IgE ratio had a mean of 42.3 (range 13.2-98.8). However, in cultures containing only naïve B cells, IL-10 failed to alter the IgE/IgG4 balance (IgG4: IgE ratio mean 2.5, range 0.71-4.5).

Conclusions: Although IL-10 differentially regulates IgE and IgG4 production in B cells in the context of accessory cells found in PBMCs, it likely does so through indirect effects on B cell isotype switching. These effects are currently being explored at the molecular level.