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Review
. 2021 Sep 29;22(19):10514.
doi: 10.3390/ijms221910514.

The Germinal Center Milieu in Rheumatoid Arthritis: The Immunological Drummer or Dancer?

Dornatien C Anang  1   2 , Giulia Balzaretti  1   2 , Antoine van Kampen  3 , Niek de Vries  1   2 , Paul L Klarenbeek  1   4
Affiliations
Review

The Germinal Center Milieu in Rheumatoid Arthritis: The Immunological Drummer or Dancer?

Dornatien C Anang et al. Int J Mol Sci. .

Abstract

Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, affecting approximately 1% of the general population. To alleviate symptoms and ameliorate joint damage, chronic use of immunosuppressives is needed. However, these treatments are only partially effective and may lead to unwanted side effects. Therefore, a more profound understanding of the pathophysiology might lead to more effective therapies, or better still, a cure. The presence of autoantibodies in RA indicates that B cells might have a pivotal role in the disease. This concept is further supported by the fact that a diverse antibody response to various arthritis-related epitopes is associated with arthritis development. In this context, attention has focused in recent years on the role of Germinal Centers (GCs) in RA. Since GCs act as the main anatomic location of somatic hypermutations, and, thus, contributing to the diversity and specificity of (auto) antibodies, it has been speculated that defects in germinal center reactions might be crucial in the initiation and maintenance of auto-immune events. In this paper, we discuss current evidence that various processes within GCs can result in the aberrant production of B cells that possess autoreactive properties and might result in the production of RA related autoantibodies. Secondly, we discuss various (pre-)clinical studies that have targeted various GC processes as novel therapies for RA treatment.

Keywords: Rheumatoid Arthritis; autoantibodies; follicular T cells; germinal centers; lymphoid organs.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Architecture and main cellular components of the germinal center. The germinal center is mainly divided into two zones; the Dark zone (DZ) where GC B cells undergo somatic hypermutation (SHM) of their immunoglobulin (Ig) genes and the light zone (LZ) where GC B cells interact with antigens presented to them by FDCs as well as T follicular helper cells (Tfh). GC: germinal center, FDCs: follicular dendritic cells.
Figure 2
Figure 2
Possible therapeutic targets on Tfh cells for the treatment of RA. Several molecules and receptors expressed on Tfh can be targeted to dampen aberrant immune responses in RA such as anti-ICOS, anti-CTLA4, anti-OX40, anti-CXCR5, Anti-CD40, IL-21 antagonist and IL-4 antagonist. CR2, complement receptor 2; FDC, follicular dendritic cell.
See this image and copyright information in PMC

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