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

Coelho FM, Natale D, Soriano SF, Hons M, Swoger J, Mayer J, Danuser R, Scandella E, Pieczyk M, Zerwes HG, Junt T, Sailer AW, Ludewig B, Sharpe J, Figge MT, Stein JV (2013) Naive B-cell trafficking is shaped by local chemokine availability and LFA-1-independent stromal interactions. Blood 121(20), 4101-4109. PubMed

Abstract

It is not known how naive B cells compute divergent chemoattractant signals of the T-cell area and B-cell follicles during in vivo migration. Here, we used two-photon microscopy of peripheral lymph nodes (PLNs) to analyze the prototype G-protein-coupled receptors (GPCRs) CXCR4, CXCR5, and CCR7 during B-cell migration, as well as the integrin LFA-1 for stromal guidance. CXCR4 and CCR7 did not influence parenchymal B-cell motility and distribution, despite their role during B-cell arrest in venules. In contrast, CXCR5 played a nonredundant role in B-cell motility in follicles and in the T-cell area. B-cell migration in the T-cell area followed a random guided walk model, arguing against directed migration in vivo. LFA-1, but not α4 integrins, contributed to B-cell motility in PLNs. However, stromal network guidance was LFA-1 independent, uncoupling integrin-dependent migration from stromal attachment. Finally, we observed that despite a 20-fold reduction of chemokine expression in virus-challenged PLNs, CXCR5 remained essential for B-cell screening of antigen-presenting cells. Our data provide an overview of the contribution of prototype GPCRs and integrins during naive B-cell migration and shed light on the local chemokine availability that these cells compute.

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doi: 10.1182/blood-2012-10-465336 PMID: 23558016