Characterization of B cells in synovial fluid and tissue from patients with JIA

Aim

The nature of B cell subsets infiltrating the synovial membrane from JIA patients is poorly defined. To this aim we performed an immunophenotypic and functional characterization of B cells in JIA patients.

Methods

MNC from synovial fluid (SF) and paired peripheral blood (PB) from 25 JIA patients and 20 age-matched controls were analyzed with multi-colour flow cytometry.

Results

SF B cells were found to be significantly enriched in CD27⁺ switch memory (sm) 1 cells and in the recently identified isotype class switch memory (CD19⁺CD27^-IgG⁺IgA⁺) B cells (sm2) compared to paired and healthy PB (P < 0.0001). CCR5, CCR8, and CCR9 expression was significantly higher on SF sm1 and sm2 B cells than on correspondent paired PB B cells (P < 0.001). Naïve (IgD⁺, CD27^-) B cells were significantly reduced in SF compared to paired and control PB (P < 0.0001). Similarly, transitional B cells (CD19⁺CD24^highCD38^highIgM^highIgD^high) were significantly less numerous in SF than in paired PB from JIA patients (P < 0.0001).

Plasma blasts were significantly enriched in SF than in paired PB (P = 0.005). ELISPOT experiments showed significantly higher proportions of CD19⁺ IgG secreting cells in SF vs paired JIA PB (P = 0.028). Histological analysis of synovial tissue sections demonstrated the presence of lymphoid aggregates containing clusters of CD20⁺ cells surrounded by CD138⁺plasmablasts/plasmacells producing predominantly IgG.

Conclusion

These findings support a model whereby memory B cells are selectively attracted through chemokine gradients to the inflamed joints of JIA patients and differentiate locally into plasmablasts/plasmacells in the absence of ectopic follicular structures.