Expression of FcRL4 defines a pro-inflammatory, RANKL-producing B cell subset in rheumatoid arthritis.

OBJECTIVES: The success of B cell targeting therapies has highlighted the importance of B cells in rheumatoid arthritis pathogenesis. We have previously shown that B cells in the RA synovium are capable of producing pro-inflammatory and bone-destructive cytokines including RANKL. Here we sought to characterise the nature and functional relevance of the RANKL-producing B cell subset in the RA synovium. METHODS: Synovial fluid and peripheral blood B cells from patients with RA were analysed by flow cytometry for markers of B cell differentiation and activation and for chemokine receptors. FcRL4(+) and FcRL4(-) B cells sorted from synovial fluid were analysed for cytokine expression using Taqman low-density arrays. Synovial tissue biopsies obtained from patients with RA were analysed by immunofluorescence for CD20, RANKL and FcRL4. FCRL4 mRNA expression was determined in synovial tissue of RA patients and non-inflammatory control subjects by real-time PCR. RESULTS: RANKL-producing B cells in RA synovial tissue and fluid were identified as belonging to a distinct subset of B cells defined by expression of the transmembrane protein FcRL4. FcRL4+ B cells express a distinct combination of cytokines and surface proteins indicating a function distinct from that of FcRL4- B cells. Notably, FcRL4+ B cells expressed high levels of TNF-α and RANKL mRNA. CONCLUSIONS: We have identified a novel pro-inflammatory B cell population in the RA synovium which is defined by expression of FcRL4 and responsible for RANKL production. This B cell population expresses high levels of CD20, and its removal by rituximab may contribute to the anti-inflammatory effect of this drug.

[Safety aspects of the practical application of a gI-negative subunit vaccine against Aujeszky's disease in swine]. / Veiligheidsaspecten van toepassing van een gI-negatief sub-unitvaccin tegen de ziekte van Aujeszky bij varkens in de praktijk.

On two farms in an area in which Aujeszky's disease is endemic, 192 pregnant sows were vaccinated with a gI-negative sub-unit vaccine against Aujeszky's disease. The rectal temperatures of the sows were recorded once daily for seven consecutive days, starting on the day of vaccination, and the vaccinated animals were observed for local and systemic reactions. The temperatures recorded did not exceed 39.8 degrees C in any case, and local or systemic reactions caused by vaccinations were not observed. One sow (0.6 per cent) aborted, but other symptoms of disease were not apparent, and there was no relationship with vaccination. In a second experiment, the carcasses of 120 pigs, vaccinated once or twice with the same vaccine, were carefully examined for local reactions. In eleven pigs (9.1 per cent) slight cicatricial reactions were visible within from 20 to 34 days after inoculation, the diameter not exceeding 1.5 cm in any of the cases. Traces of vaccination were no longer perceptible within 84 days after vaccination. The vaccine was found to be very safe for pregnant sows under field conditions.

[Field experience using an inactivated vaccine in Aujeszky's disease vaccination of cattle (author's transl)]. / Praktijk-ervaringen met een geïnactiveerd vaccin voor de enting van runderen tegen de ziekte van Aujeszky.

In the autumn of 1979, approximately, 400 animals on twenty farms were inoculated twice against Aujeszky's disease using an inactivated vaccine in a practice in the Achterhoek (province of Gelderland). The animals vaccinated were mainly yearlings and heifers on farms on which cattle and pigs could not be effectively separated. Adverse reactions to vaccination, other than a slight to moderate increase in body temperature, were not observed. Outbreaks did not occur in vaccinated cattle during the 1979-1980 winter season; on the other hand, Aujeszky's disease was observed in the pigs on a number of farms. The serological effects of vaccination were followed up in forty-one animals on sixteen farms. Very high antibody titres were attained, particularly after the second vaccination. Antibody titres continued to be recorded after twelve months in a number of the animals followed.