Background/Purpose: Double negative (CD19+IgD-CD27-) B cells have been reported to be part of human memory B cell compartment. Detailed studies of DN B cells in autoimmune diseases like rheumatoid arthritis (RA) and during different B cell targeted therapies are sparse. Therefore we analyzed in detail these cells in RA patients under IL-6 R inhibitor tocilizumab.

Methods: DN B cells were phenotypically analyzed from RA patients (mean age ~61 years) at baseline and 12, 24 and 48 weeks after tocilizumab treatment. Additionally, single B cell sorting technology followed by nested PCR approach was used to study mutational pattern of Ig- receptors VH genes. 

Results: The phenotypic analysis of DN B cells in RA patients (n=33) and healthy individuals (n=22) showed a significantly expanded population (p=0.034) of these cells in RA. DN B cells showed a heterogeneous mixture of IgA, IgG and IgM expressing cells with clear dominance of IgG+ cells. Pre-therapy analysis of rearranged IgR sequences from patients (n=7) revealed comparable but diversified mutational pattern of DN B cells comprising mutated and non-mutated sequences. During tocilizumab, DN B cells showed significantly reduced mutational frequency in their Ig-receptors with a marked reduction of the mutated Ig-receptors at week 12 (p<0.0001), 24 (p=0.0147) and 48 (p=0.0017) during treatment.

Conclusion: Our data suggest expanded DN B cells population in RA which are susceptible to IL-6R inhibition in vivo by tocilizumab. Particularly, acquisition of mutations was substantially altered in DN B cells. These results indicate that DN B cells have dependence on the IL6/IL6R system for differentiation in vivo which can be modulated by anti-IL6R therapy.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/il-6-receptor-inhibition-by-tocilizumab-modulates-double-negative-cd19igd-cd27-b-cells-in-ra/