Circulating plasmablasts/plasmacells as a source of anticitrullinated protein antibodies in patients with rheumatoid arthritis.

OBJECTIVE: To study the characteristics and phenotype of anticitrullinated protein antibody (ACPA)-specific B cells in peripheral blood of patients with rheumatoid arthritis (RA).
METHODS: Peripheral blood B cells from ACPA-positive patients with RA were cultured with or without stimulating factors. Following culture, supernatants were assessed for the presence of ACPA-IgG and non-specific total IgG by ELISA.
RESULTS: Following stimulation, ACPA were detectable in up to 100% of culture wells. Of interest, ACPA were also produced spontaneously by unstimulated peripheral blood mononuclear cells. In both cases, the average ACPA titre per culture well correlated with ACPA serum titres. No ACPA production was detectable in B cell cultures from ACPA-negative patients with RA or healthy controls. Importantly, FACS-sorting experiments located spontaneous ACPA production to the CD20 negative B cell population corresponding to circulating plasmablasts/cells.
CONCLUSIONS: ACPA-specific peripheral blood B cells are not confined to the CD20 positive memory pool, as circulating plasmablasts/cells spontaneously producing ACPA are also readily detectable. The latter points to an ongoing B cell immune response against citrullinated proteins and contrasts conventional immune responses against, for example, vaccines, where antigen-specific plasmablasts appear in peripheral blood only shortly after vaccination. These circulating, ACPA-specific plasmablasts/cells might represent targets for novel therapeutic interventions.