Regulation of B lymphocytes and plasma cells by innate immune mechanisms and stromal cells in rheumatoid arthritis

Abstract

B cells mediate multiple functions that influence immune and inflammatory responses in rheumatoid arthritis. Production of a diverse array of autoantibodies can happen at different stages of the disease, and are important markers of disease outcome. In turn, the magnitude and quality of acquired humoral immune responses is strongly dependent on signals delivered by innate immune cells. Additionally, the milieu of cells and chemokines that constitute a niche for plasma cells rely strongly on signals provided by stromal cells at different anatomical locations and times. The chronic inflammatory state therefore importantly impacts the developing humoral immune response and its intensity and specificity. We focus this review on B cell biology and the role of the innate immune system in the development of autoimmunity in patients with rheumatoid arthritis.

Keywords::

• autoantibodies
• B cells
• inflammation
• innate immunity
• plasma cells

Acknowledgements

The authors thank Drs. Elizabeth M Johnson and David DiLillo for their input and comments.

Financial & competing interests disclosure

This work was supported by National Institutes of Health AR049010. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Inflammatory signals can alter many B-cell functions, from selection of autoreactive clones to survival of plasma cells.

• B cells contribute to rheumatoid arthritis (RA) pathogenesis through production of autoantibodies, and these autoantibodies are important factors in the formation of immune complexes and triggering undesired activation of inflammatory cascades.

• It is very likely that B cells play additional roles to capture, process and present antigen, as well as to alter the local cytokine/chemokine microenvironment.

• Regulatory B cells have potent immunosuppressive capacities that can modulate RA development.

• B cells can interact with many nonlymphoid cells. The innate immune system, with many newly identified cell types in the last few years, can shape the type and intensity of B-cell responses, especially the production of antibodies and autoantibodies.

• Chronic inflammatory conditions lead to imbalanced immune system responses. Innate immune cells and stromal cells readily respond to many inflammatory signals, and their co-localization with B and T cells can support the amplification and perpetuation of inflammation.

• The few existing therapies in RA targeting B cells are focused on depletion strategies. New therapies and approaches are under development targeting B-cell subsets and inhibiting B-cell functions without depletion.

• Manipulating the interaction between inflammatory signals and innate immune responses could help to suppress undesired B-cell responses to block disease progression.

Notes