Regulatory B cell processes appear aberrant in lupus

Reuters Health Information: Regulatory B cell processes appear aberrant in lupus

Regulatory B cell processes appear aberrant in lupus

Last Updated: 2016-03-17

By David Douglas

NEW YORK (Reuters Health) - Disruption of the processes that govern the differentiation of immature B cells into regulatory B cells (Bregs) that restrain inflammation may contribute to the pathogenesis of systemic lupus erythematosus (SLE), according to researchers at University College London.

Senior author Dr. Claudia Mauri, said in a statement, "Our study shows for the first time that the overproduction of (interferon-alfa) by hyperactivated plasmacytoid dendritic cells (pDCs) in lupus patients is the consequence of the lack of suppressive regulatory B cells. The uncontrolled production of IFN-alpha causes an increase of antibody-producing B cells and suppresses the division and appearance of regulatory B cells."

In healthy subjects, the researchers found that pDCs drive the differentiation of immature B cells into interleukin-10 (IL-10)-producing Breg cells and plasmablasts via processes including the release of IFN-alpha. Conversely, Breg cells restrain IFN-alpha production by pDCs via IL-10 release.

Some SLE patients respond to rituximab and some don't and to find out whether these processes might influence its action, the investigators went on to analyze immune cells and genetic activity from nearly 100 healthy volunteers and 200 SLE patients.

The team found that in SLE, pDCs promoted plasmablast differentiation but failed to induce Breg cells. This was also found in healthy B cells exposed to high levels of INF-alpha. However, in SLE patients who responded to rituximab, Breg cell interactions and other processes were normalized.

The study appeared online March 8 in the journal Immunity.

Commenting on the findings by email, lead author Dr. Madhvi Menon told Reuters Health, "Our study suggests that testing patients prior to commencing B cell depletion therapy for IFN-alpha-induced signature levels could help predict response to therapy."

In fact, she concluded, "New strategies to harness the suppressive capacity of regulatory B cells will be the focus of future work."

The Wellcome Trust supported this research. The authors reported no disclosures.

SOURCE: http://bit.ly/1S6GoVt

Immunity 2016.

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