UCSF

Effective surveillance of the lymph-borne milieu of foreign antigens requires the recirculation of lymphocytes. Their patrol takes them from the blood, into secondary lymphoid organs, and into lymph, from which they ultimately return to the blood. Much has been discovered about how this process unfolds at the microanatomic and molecular levels. However, understanding of how the mechanisms involved differ for mucosal immune tissues continues to develop.

Peyer's patches (PPs) play a central role in supporting B cell responses against intestinal antigens, yet the factors controlling B cell passage through these mucosal lymphoid tissues are incompletely understood. Here we report that, in mixed chimeras, CXCR4-deficient B cells accumulate in PPs compared to their representation in other lymphoid tissues. CXCR4-deficient B cells egress from PPs more slowly than wild-type cells while CXCR5-deficient cells egress more rapidly. The CXCR4 ligand, CXCL12, is expressed by cells adjacent to lymphatic endothelial cells in a zone that abuts but minimally overlaps with the CXCL13⁺ follicle. CXCR4-deficient B cells show reduced localization to these CXCL12⁺ peri-lymphatic zones whereas CXCR5-deficient B cells preferentially localize in these regions. By photoconverting KikGR-expressing cells within surgically exposed PPs, we provide evidence that naïve B cells transit PPs with an approximate residency half-life of 10 h. When CXCR4 is lacking, KikGR⁺ B cells show a delay in PP egress. In summary, we identify a CXCL12^hi peri-lymphatic zone in PPs that plays a role in overcoming CXCL13-mediated retention to promote B cell egress from these gut-associated lymphoid tissues.