The cellular homeostasis of lymphoid tissues is determined by the continuous interactions
of mobile hematopoietic cells within specialized microenvironments created by sessile
stromal cells. In contrast to the lymph nodes and mucosal lymphoid tissues with well-defined
entry and exit routes, the movement of leukocytes in the peritoneal cavity is largely
unknown. In this study, we report that, in addition to the omental milky spots and
fat-associated lymphoid clusters, in mice, the serous surface of the mesenteric adipose
streaks contains lymphocyte-rich organoids comprised of a highly compacted leaf-like
part connected to the adipose tissue that can also efficiently bind B cells and high-grade
B cell lymphoma (diffuse large B cell lymphoma) cells. Denoted as foliate lymphoid
aggregates (FLAgs), these structures show incomplete T/B segregation and a partially
differentiated stromal architecture. LYVE-1-positive macrophages covering FLAgs efficiently
bind i.p. injected normal B cells as well as different types of diffuse large B cell
lymphoma cells. Within FLAgs, the lymphocytes compartmentalize according to their
chemokine receptor pattern and subsequently migrate toward the mesenteric lymph nodes
via the mesenteric lymphatic capillaries. The blood supply of FLAgs includes short
vascular segments displaying peripheral lymph node addressin, and the extravasation
of lymphocytes to the omental and mesenteric adipose tissues is partly mediated by
L-selectin. The appearance of i.p. injected cells in mesenteric lymph nodes suggests
that the mesentery-associated lymphatics may also collect leukocytes from the fat-associated
lymphoid clusters and FLAgs, thus combining the mucosal and serous exit of mobile
leukocytes and increasing the range of drainage sites for the peritoneal expansion
of lymphoid malignancies.