Expression of Membrane-Bound CC Chemokine Ligand 20 on Follicular T Helper Cells in T–B-Cell Conjugates

Abstract

The CC chemokine receptor 6 (CCR6) and its sole chemokine ligand CC chemokine ligand 20 (CCL20) display an emerging role in the coordination of humoral immune responses. Recent studies demonstrate a role of this chemokine axis in the migration of B cells to key immunological sites during an immune response, and facilitating the generation of high-quality antibodies. Very little, however, is known about CCL20 and its role in these functions. We undertook a preliminary investigation into the expression and function of CCL20 and demonstrate its well-noted upregulation in the spleen during immunization. Furthermore, we show that most follicular T helper (Tfh) cells can be CCR6+ and can produce CCL20. Surprisingly, CCL20 cannot only be found in the cytoplasm but also on the surface of these cells and their precursors. Analysis of T–B-cell conjugates revealed that mature Tfh cells, but not their precursors, are highly enriched in the conjugates. Further functional studies are needed to unravel the precise role of CCL20 in coordinating T and B cell interactions during the humoral immune response.

Ethanol consumption inhibits TFH cell responses and the development of autoimmune arthritis

“…Further antibodies: CD3 (clone 145-2C11), CD8α (clone 53-6.7), CD11b (clone M1/70), CD11c (clone N418), CD45 (clone 30-F11), CD138 (clone 281-2), F4/80 (clone BM8), Fas (clone 15A7), Ly6c (clone HK1.4), Ly6G (clone 1A8), MHCII (clone M5/114.15.2), TACI (clone ebio8F10-3), and Siglec F (clone ES22-10D8), PNA-biotin (Vector), Streptavidin-PE/CF594 (BD), NKp46 (clone 29A1.4), CD49 (clone DX5), CD16 (clone 93), IL-4 (clone 11B11), IL-17 (clone TC11-18H10.1), IL-9 (clone RM9A4). T FH :B cell doublet gating strategy is adopted from previously published article 69 and is shown in Supplementary Fig. 3f.…”

CC chemokine receptor 6 (CCR6) in the pathogenesis of systemic lupus erythematosus

“…CCR6 and CCL20 may assist with positioning T FH and B cells at the T-B cell border and contributing to the "quality" of the T-B cell synapse. 8 The role of the possible raised CCR6 on B-cell subsets in SLE patients 66 remains a mystery at this stage. However, Elgueta et al 75 have shown that CCR6 expression on memory B cells remains important for proper localization and function of these cells in lymphoid organs, and CCR6 has been identified as a marker of B cells undergoing memory B-cell differentiation.…”

“…Recently, a small percentage of T FH cells have been shown to be CCR6 + . 8 In SLE studies, circulating T FH cells-rather than tissue T FH cells-have been commonly studied owing to ease of acquisition. They are thought to have originated from, and be functionally similar to, their GC compartment counterparts, although have discernible differences in their epigenetic profile.…”

“…7 At a cellular level, it is expressed by T cells (including T H 17 cells), macrophages, neutrophils and endothelial cells. 8,9 Together with CCR6, the CCR6-CCL20 axis has been implicated in a wide range of autoimmune diseases, cancers and viral infections such as HIV infections. [10][11][12] More recently, however, CCR6 has been implicated in coordinating humoral immune responses.…”

“…In secondary lymphoid organs such as lymph nodes, CCL20 can be detected, whereas in the spleen, its presence is below the detection threshold in bulk analysis of the entire organ 7 . At a cellular level, it is expressed by T cells (including T H 17 cells), macrophages, neutrophils and endothelial cells 8,9 . Together with CCR6, the CCR6–CCL20 axis has been implicated in a wide range of autoimmune diseases, cancers and viral infections such as HIV infections 10–12 …”