Analyzing the in vivo contribution of G-protein coupled receptors for naive B cell trafficking in lymph nodes (44.23)

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Abstract B cell motility within lymphoid tissue is precisely orchestrated by G-protein-coupled receptors (GPCRs) of the chemokine receptor family and other GPCRs, including the recently described 7α,25-dihydroxycholesterol receptor Ebi2. Here, we performed an exhaustive twophoton microscopy (2PM) analysis of the contribution of the chemokine receptors CXCR4, CXCR5 and CCR7, as well as Ebi2, during the dynamic migration of naïve B cells inside peripheral lymph nodes (PLNs) and the kinetics of B cell accumulation from the T cell area in B cell follicles. Using the intravital 2PM model of murine popliteal PLNs paired with genetic and pharmacological inhibition of GPCRs and their ligands, we observed a non-redundant role for CXCR5 for dynamic B cell motility in the T cell area and B cell follicles, while the functional absence of CXCR4 and CCR7 did not influence B cell migration parameters. Although CXCR5 was central for efficient B cell accumulation in B cell follicles, we did not find evidence for directed migration of T cell area-borne B cells towards B cell follicles, supporting a chemokinetic, and not chemotactic, role for the CXCR5 ligand CXCL13 during this process. Lack of Ebi2 confined B cells to the central part of B cell follicles, resulting in higher average migration velocities as compared to wild type B cells. In summary, our data provide novel insight into the contribution of GPCRs during the dynamic migration of naïve B cells in non-inflamed and inflamed PLNs.