Cutting Edge: The B Cell Chemokine CXC Chemokine Ligand 13/B Lymphocyte Chemoattractant Is Expressed in the High Endothelial Venules of Lymph Nodes and Peyer’s Patches and Affects B Cell Trafficking Across High Endothelial Venules

Abstract

While CCR7 ligands direct T cell trafficking into lymph nodes (LNs) and Peyer’s patches (PPs), chemokines that regulate B cell trafficking across high endothelial venules (HEVs) remain to be fully elucidated. Here we report that CXC chemokine ligand (CXCL)13 (B lymphocyte chemoattractant) is detected immunohistologically in the majority of HEVs in LNs and PPs of nonimmunized mice. Systemically administered anti-CXCL13 Ab bound to the surface of ∼50% of HEVs in LNs and PPs, but not to other types of blood vessels, indicating that CXCL13 is expressed in the HEV lumen. In CXCL13-null mice, B cells rarely adhered to PP HEVs, whereas T cells did efficiently. Superfusion of CXCL13-null PPs with CXCL13 restored the luminal presentation of CXCL13 and also B cell arrest in PP HEVs at least partially. Collectively, these results indicate that CXCL13 expressed in the HEV lumen plays a crucial role in B cell trafficking into secondary lymphoid tissues such as PPs.

Aberrant B1 cell migration into the thymus results in activation of CD4 T cells through its potent antigen‐presenting activity in the development of murine lupus

“…BLC produced by infiltrated CD11c + DC in enlarged PVS might be transported to the luminal surfaces of HEV, as indicated by Ebisuno et al [18]. We also previously demonstrated that B1 cells were chemoattracted towards BLC much more efficiently than B2 cells [8].…”

CXCR5+ CCR7– CD8 T cells are early effector memory cells that infiltrate tonsil B cell follicles

“…One may speculate that these cells are previously primed longterm effector memory cells which may re-enter the B cell follicles directly through HEV using CD62L, as CXCL13 can be expressed on the surface of HEV [34]. Alternatively, the blood CXCR5 + CD8 T cells may be cells that have recently left B cell follicles, or circulate between follicles in different secondary lymphoid organs.…”

Naive B-cell trafficking is shaped by local chemokine availability and LFA-1–independent stromal interactions

“…Also, while it is well established that LFA-1 and its ligand ICAM-1 expressed on stromal cell networks contribute to parenchymal B-cell motility, 3 it remains unclear whether blocking of these interactions affects the guidance function of FRCs and FDCs during B-cell migration and their microenvironmental distribution. Finally, although homeostatic chemokine levels are strongly suppressed in inflamed PLNs, 1,2,15,16 naive B cells retain the capacity to engage with antigen-presenting FDCs through unknown mechanisms. 3,17 Here, we used live two-photon (2-P) microscopy and applied a combined genetic and pharmacologic approach to functionally address chemokine availability and evaluate the contribution of CXCR5, CCR7, and CXCR4 during dynamic B-cell motility, including gradient sensing within the T-and B-cell areas.…”

“…Thus, arrest of bloodborne B cells in high endothelial venules requires binding of the chemokine receptors CXCR4, CCR7, and, to a minor extent, CXCR5 to their respective ligands CXCL12, CCL19/CCL21, and CXCL13, leading to LFA-1 activation and binding to ICAM-1 and ICAM-2. [1][2][3] Studies in mice have shown that B cells accumulate from their entry point in the T-cell area in 1 of approximately 7-35 B-cell follicles located in the peripheral lymph node (PLN) cortex. 4,5 During their migration inside lymphoid tissue, B cells use the ICAM-1-expressing fibroblastic reticular cell (FRC) network of the T-cell area and the follicular dendritic cell (FDC) network in follicles as guidance structures.…”