gms | German Medical Science

Introduction: FLS are capable of inducing class switch recombination (CSR) in naïve B cells. Isotype switch towards IgG is heavily favored. These IgG switched B cells are highly activated and secrete large amounts of IgG. Contrary to this IgG induction, FLS are also capable of supporting a non-naïve, IgD+ B cell population, that is driven to IgD secretion through activation by the FLS. These IgD+ B cells are not driven towards CSR. There has been evidence, that FLS react to the presence of IgD. Here, we studied the interaction between FLS and Immunoglobulins in the context of FLS dependent B cell activation and CSR induction.

Methods: Peripheral total IgD+ B cells (DBC) and naïve B cells (NBC) were isolated from healthy donors by MACS and co-cultured with or w/o SFs in the presence of IL-4. After 8 days secreted IgG, IgM and IgD were measured by ELISA. FLS were treated with or without IgG, IgM or IgD for 3 days. CD40L, APRIL and MHC2 surface expression was determined by flow cytometry.

Results: After 8 days, DBC co-cultures produce 21.7 ng/mL +/- 11.1 ng/mL of IgM, while NBC cultures produce 0.7 ng/mL +/- 0.9 ng/mL (p = 0.03). IgD concentrations are 33.7 ng/mL +/- 19.5 ng/mL in DBC cultures while no IgD is detectable in NBC cultures (p = 0.04). DBCs produce 31.7 ng/mL +/- 9.9 ng/mL of IgG while NBC cultures produce 61.8 ng/mL +/- 21.3 ng/mL of IgG (p = 0.05).

CD55+ FLS treated with IgD for 3 days show significantly decreased CD40L surface expression compared to untreated controls. Relative fluorescence median is reduced to 79% +/- 26% of controls (p = 0.03). Treatment with IgG or IgM causes no significant shift in CD40L expression. MHC2 surface expression is also reduced to 79% +/- 25% in IgD treated FLS compared to untreated controls (p = 0.01) while IgG and IgM treatment has no effect on MHC2 surface expression. A statistical trend was detected for IgD treatment, increasing APRIL surface expression to 144% +/- 73% (p = 0.08). IgG and IgM treatment have no effect on APRIL expression.

Conclusion: IgD appears to downregulate CD40L and MHC2 expression on FLS, which suggests a decreased potential to induce CSR in B cells, directly or through T cells. At the same time APRIL is upregulated in the presence of IgD, possibly leading to increased capability to support and activate B cells. IgG and IgM have no effect on CD40L, MHC2 or APRIL expression on FLS. IgD seems to play a role in the regulation of FLS dependent B cell activation and CSR induction.

Disclosures: None declared